Gut CD4+ T cell phenotypes are a continuum molded by microbes, not by TH archetypes
CD4 + effector lymphocytes (T eff ) are traditionally classified by the cytokines they produce. To determine the states that T eff cells actually adopt in frontline tissues in vivo, we applied single-cell transcriptome and chromatin analyses to colonic T eff cells in germ-free or conventional mice o...
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| Published in | Nature immunology Vol. 22; no. 2; pp. 216 - 228 |
|---|---|
| Main Authors | , , , , , , , , , , , |
| Format | Journal Article |
| Language | English |
| Published |
New York
Nature Publishing Group US
01.02.2021
Nature Publishing Group |
| Subjects | |
| Online Access | Get full text |
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| Abstract | CD4
+
effector lymphocytes (T
eff
) are traditionally classified by the cytokines they produce. To determine the states that T
eff
cells actually adopt in frontline tissues in vivo, we applied single-cell transcriptome and chromatin analyses to colonic T
eff
cells in germ-free or conventional mice or in mice after challenge with a range of phenotypically biasing microbes. Unexpected subsets were marked by the expression of the interferon (IFN) signature or myeloid-specific transcripts, but transcriptome or chromatin structure could not resolve discrete clusters fitting classic helper T cell (T
H
) subsets. At baseline or at different times of infection, transcripts encoding cytokines or proteins commonly used as T
H
markers were distributed in a polarized continuum, which was functionally validated. Clones derived from single progenitors gave rise to both IFN-γ- and interleukin (IL)-17-producing cells. Most of the transcriptional variance was tied to the infecting agent, independent of the cytokines produced, and chromatin variance primarily reflected activities of activator protein (AP)-1 and IFN-regulatory factor (IRF) transcription factor (TF) families, not the canonical subset master regulators T-bet, GATA3 or RORγ.
Helper T cell subsets are characterized functionally by the cytokines they produce. Benoist and colleagues demonstrate that in vivo helper T cells do not manifest as discrete helper subsets but rather form a continuum shaped by microbial exposure. |
|---|---|
| AbstractList | CD4
+
effector lymphocytes (Teff) are traditionally classified by the cytokines they produce. To determine the states that Teff actually adopt in frontline tissues
in vivo
, we applied single-cell transcriptome and chromatin analysis on colonic Teff cells, in germ-free or conventional mice, or after challenge with a range of phenotypically biasing microbes. Subsets were marked by expression of interferon-signature or myeloid-specific transcripts, but transcriptome or chromatin structure could not resolve discrete clusters fitting classic T
H
subsets. At baseline or at different times of infection, transcripts encoding cytokines or proteins commonly used as T
H
markers distributed in a polarized continuum, which was also functionally validated. Clones derived from single progenitors gave rise to both IFN-γ and IL17-producing cells. Most transcriptional variance was tied to the infecting agent, independent of the cytokines produced, and chromatin variance primarily reflected activity of AP1 and IRF transcription factor families, not the canonical subset master regulators T-bet, GATA3, RORγ. CD4+ effector lymphocytes (Teff) are traditionally classified by the cytokines they produce. To determine the states that Teff cells actually adopt in frontline tissues in vivo, we applied single-cell transcriptome and chromatin analyses to colonic Teff cells in germ-free or conventional mice or in mice after challenge with a range of phenotypically biasing microbes. Unexpected subsets were marked by the expression of the interferon (IFN) signature or myeloid-specific transcripts, but transcriptome or chromatin structure could not resolve discrete clusters fitting classic helper T cell (TH) subsets. At baseline or at different times of infection, transcripts encoding cytokines or proteins commonly used as TH markers were distributed in a polarized continuum, which was functionally validated. Clones derived from single progenitors gave rise to both IFN-γ- and interleukin (IL)-17-producing cells. Most of the transcriptional variance was tied to the infecting agent, independent of the cytokines produced, and chromatin variance primarily reflected activities of activator protein (AP)-1 and IFN-regulatory factor (IRF) transcription factor (TF) families, not the canonical subset master regulators T-bet, GATA3 or RORγ.Helper T cell subsets are characterized functionally by the cytokines they produce. Benoist and colleagues demonstrate that in vivo helper T cells do not manifest as discrete helper subsets but rather form a continuum shaped by microbial exposure. CD4 + effector lymphocytes (T eff ) are traditionally classified by the cytokines they produce. To determine the states that T eff cells actually adopt in frontline tissues in vivo, we applied single-cell transcriptome and chromatin analyses to colonic T eff cells in germ-free or conventional mice or in mice after challenge with a range of phenotypically biasing microbes. Unexpected subsets were marked by the expression of the interferon (IFN) signature or myeloid-specific transcripts, but transcriptome or chromatin structure could not resolve discrete clusters fitting classic helper T cell (T H ) subsets. At baseline or at different times of infection, transcripts encoding cytokines or proteins commonly used as T H markers were distributed in a polarized continuum, which was functionally validated. Clones derived from single progenitors gave rise to both IFN-γ- and interleukin (IL)-17-producing cells. Most of the transcriptional variance was tied to the infecting agent, independent of the cytokines produced, and chromatin variance primarily reflected activities of activator protein (AP)-1 and IFN-regulatory factor (IRF) transcription factor (TF) families, not the canonical subset master regulators T-bet, GATA3 or RORγ. Helper T cell subsets are characterized functionally by the cytokines they produce. Benoist and colleagues demonstrate that in vivo helper T cells do not manifest as discrete helper subsets but rather form a continuum shaped by microbial exposure. CD4+ effector lymphocytes (Teff) are traditionally classified by the cytokines they produce. To determine the states that Teff cells actually adopt in frontline tissues in vivo, we applied single-cell transcriptome and chromatin analyses to colonic Teff cells in germ-free or conventional mice or in mice after challenge with a range of phenotypically biasing microbes. Unexpected subsets were marked by the expression of the interferon (IFN) signature or myeloid-specific transcripts, but transcriptome or chromatin structure could not resolve discrete clusters fitting classic helper T cell (TH) subsets. At baseline or at different times of infection, transcripts encoding cytokines or proteins commonly used as TH markers were distributed in a polarized continuum, which was functionally validated. Clones derived from single progenitors gave rise to both IFN-γ- and interleukin (IL)-17-producing cells. Most of the transcriptional variance was tied to the infecting agent, independent of the cytokines produced, and chromatin variance primarily reflected activities of activator protein (AP)-1 and IFN-regulatory factor (IRF) transcription factor (TF) families, not the canonical subset master regulators T-bet, GATA3 or RORγ.CD4+ effector lymphocytes (Teff) are traditionally classified by the cytokines they produce. To determine the states that Teff cells actually adopt in frontline tissues in vivo, we applied single-cell transcriptome and chromatin analyses to colonic Teff cells in germ-free or conventional mice or in mice after challenge with a range of phenotypically biasing microbes. Unexpected subsets were marked by the expression of the interferon (IFN) signature or myeloid-specific transcripts, but transcriptome or chromatin structure could not resolve discrete clusters fitting classic helper T cell (TH) subsets. At baseline or at different times of infection, transcripts encoding cytokines or proteins commonly used as TH markers were distributed in a polarized continuum, which was functionally validated. Clones derived from single progenitors gave rise to both IFN-γ- and interleukin (IL)-17-producing cells. Most of the transcriptional variance was tied to the infecting agent, independent of the cytokines produced, and chromatin variance primarily reflected activities of activator protein (AP)-1 and IFN-regulatory factor (IRF) transcription factor (TF) families, not the canonical subset master regulators T-bet, GATA3 or RORγ. |
| Author | Schmutz, Hugo Vijaykumar, Brinda Chowdhary, Kaitavjeet Schnell, Alexandra Benoist, Christophe Willie, Elijah Thakore, Pratiksha I. Mostafavi, Sara LeGros, Graham Mathis, Diane Kiner, Evgeny Chandler, Jodie |
| AuthorAffiliation | 4 Malaghan Institute of Medical Research, Wellington, New Zealand 3 Bioinformatics Program, University of British Columbia, Vancouver, Canada 7 Canadian Institute for Advanced Research, Toronto, Canada 6 Departments of Statistics and Medical Genetics, University of British Columbia, Vancouver, Canada 2 Evergrande Center for Immunologic Diseases, Harvard Medical School and Brigham and Women’s Hospital, Boston, USA 8 Vector Institute, Toronto, Canada 1 Department of Immunology, Harvard Medical School 5 Klarman Cell Observatory, Broad Institute of MIT and Harvard, Cambridge, USA 9 Present Address: Immunai, New York, NY, USA |
| AuthorAffiliation_xml | – name: 2 Evergrande Center for Immunologic Diseases, Harvard Medical School and Brigham and Women’s Hospital, Boston, USA – name: 1 Department of Immunology, Harvard Medical School – name: 3 Bioinformatics Program, University of British Columbia, Vancouver, Canada – name: 7 Canadian Institute for Advanced Research, Toronto, Canada – name: 8 Vector Institute, Toronto, Canada – name: 9 Present Address: Immunai, New York, NY, USA – name: 5 Klarman Cell Observatory, Broad Institute of MIT and Harvard, Cambridge, USA – name: 6 Departments of Statistics and Medical Genetics, University of British Columbia, Vancouver, Canada – name: 4 Malaghan Institute of Medical Research, Wellington, New Zealand |
| Author_xml | – sequence: 1 givenname: Evgeny surname: Kiner fullname: Kiner, Evgeny organization: Department of Immunology, Harvard Medical School, Evergrande Center for Immunologic Diseases, Harvard Medical School and Brigham and Women’s Hospital, Immunai – sequence: 2 givenname: Elijah surname: Willie fullname: Willie, Elijah organization: Bioinformatics Program, University of British Columbia – sequence: 3 givenname: Brinda surname: Vijaykumar fullname: Vijaykumar, Brinda organization: Department of Immunology, Harvard Medical School, Evergrande Center for Immunologic Diseases, Harvard Medical School and Brigham and Women’s Hospital – sequence: 4 givenname: Kaitavjeet surname: Chowdhary fullname: Chowdhary, Kaitavjeet organization: Department of Immunology, Harvard Medical School, Evergrande Center for Immunologic Diseases, Harvard Medical School and Brigham and Women’s Hospital – sequence: 5 givenname: Hugo surname: Schmutz fullname: Schmutz, Hugo organization: Department of Immunology, Harvard Medical School, Evergrande Center for Immunologic Diseases, Harvard Medical School and Brigham and Women’s Hospital – sequence: 6 givenname: Jodie surname: Chandler fullname: Chandler, Jodie organization: Malaghan Institute of Medical Research – sequence: 7 givenname: Alexandra surname: Schnell fullname: Schnell, Alexandra organization: Evergrande Center for Immunologic Diseases, Harvard Medical School and Brigham and Women’s Hospital – sequence: 8 givenname: Pratiksha I. surname: Thakore fullname: Thakore, Pratiksha I. organization: Klarman Cell Observatory, Broad Institute of MIT and Harvard – sequence: 9 givenname: Graham surname: LeGros fullname: LeGros, Graham organization: Malaghan Institute of Medical Research – sequence: 10 givenname: Sara surname: Mostafavi fullname: Mostafavi, Sara organization: Departments of Statistics and Medical Genetics, University of British Columbia, Canadian Institute for Advanced Research, Vector Institute – sequence: 11 givenname: Diane orcidid: 0000-0002-6110-4626 surname: Mathis fullname: Mathis, Diane email: cbdm@hms.harvard.edu organization: Department of Immunology, Harvard Medical School, Evergrande Center for Immunologic Diseases, Harvard Medical School and Brigham and Women’s Hospital – sequence: 12 givenname: Christophe orcidid: 0000-0003-1172-6555 surname: Benoist fullname: Benoist, Christophe email: cbdm@hms.harvard.edu organization: Department of Immunology, Harvard Medical School, Evergrande Center for Immunologic Diseases, Harvard Medical School and Brigham and Women’s Hospital |
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| Cites_doi | 10.1016/j.cell.2018.05.060 10.1016/j.immuni.2019.03.004 10.1016/0167-5699(95)80004-2 10.1126/science.1260668 10.1038/nature11981 10.1038/ncomms11627 10.1126/science.aaa1934 10.4049/jimmunol.114.2_Part_2.747 10.4049/jimmunol.138.6.1674 10.1038/nature14590 10.1016/j.coi.2012.02.001 10.1038/nrmicro3315 10.1038/nmeth.4401 10.4049/jimmunol.136.7.2348 10.1214/aos/1176346577 10.1093/bioinformatics/bty491 10.1038/nature09447 10.1016/j.cell.2018.12.036 10.1016/j.cell.2015.12.032 10.1016/j.immuni.2019.01.001 10.1093/bioinformatics/bty430 10.1016/j.immuni.2019.03.009 10.1038/ni.2416 10.1016/j.immuni.2008.05.009 10.1073/pnas.1311557110 10.4049/jimmunol.0903505 10.1146/annurev.immunol.021908.132710 10.1016/j.cell.2019.08.006 10.1016/j.cell.2018.05.061 10.1038/ni.3247 10.1038/s41590-019-0398-x 10.1016/j.immuni.2015.01.013 10.1016/j.immuni.2019.05.004 10.1038/nbt.4096 10.1016/j.immuni.2011.09.019 10.1146/annurev.immunol.18.1.451 10.1038/s41586-018-0414-6 10.1038/nri3365 10.4049/jimmunol.156.9.3321 10.1093/bioinformatics/btv325 10.1038/s41586-020-2056-8 10.1101/gr.192237.115 10.1093/bioinformatics/btr406 10.1016/0092-8674(91)90448-8 10.1038/s41467-020-15543-y 10.1186/s13059-018-1603-1 10.1038/nmeth.4380 10.1126/science.aaa9420 10.1146/annurev-immunol-031210-101400 10.1126/science.1178334 10.1038/ni.1899 10.1182/blood-2008-05-078154 10.3389/fimmu.2014.00630 10.1038/ni1539 10.1038/s41586-018-0436-0 10.1016/0167-5699(88)91308-4 10.1016/j.cell.2012.09.016 10.1016/j.cell.2018.11.043 10.1126/science.aan6828 10.1016/j.immuni.2019.05.014 10.1101/461228 10.1002/0471142735.im1912s55 10.1101/2020.01.23.911966 10.1002/cyto.a.24027 |
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| Notes | ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 14 content type line 23 CONTRIBUTIONS E.K. and E.W. performed experiments. E.K., B.V., K.C., H.S., S.M. and C.B. analysed and interpreted data. A.S., P.I.T., J.C. and G.L. provided data or reagents. E.K., S.M., D.M. and C.B. designed the study and wrote the manuscript. |
| ORCID | 0000-0002-6110-4626 0000-0003-1172-6555 |
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| PublicationDateYYYYMMDD | 2021-02-01 |
| PublicationDate_xml | – month: 2 year: 2021 text: 20210200 |
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| PublicationPlace | New York |
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| PublicationTitle | Nature immunology |
| PublicationTitleAbbrev | Nat Immunol |
| PublicationYear | 2021 |
| Publisher | Nature Publishing Group US Nature Publishing Group |
| Publisher_xml | – name: Nature Publishing Group US – name: Nature Publishing Group |
| References | Korn, Bettelli, Oukka, Kuchroo (CR5) 2009; 27 Arazi (CR33) 2019; 20 Alexander (CR37) 2018; 562 Stoeckius (CR34) 2017; 14 Collins (CR53) 2014; 12 Araneo, Marrack, Kappler (CR1) 1975; 114 Jabeen, Kaplan (CR6) 2012; 24 Zilionis (CR47) 2019; 50 Omenetti (CR24) 2019; 51 Stubbington, Rozenblatt-Rosen, Regev, Teichmann (CR15) 2017; 358 Kowalczyk (CR62) 2015; 25 Kelso (CR12) 1995; 16 CR35 Mostafavi (CR50) 2016; 164 Becattini (CR42) 2015; 347 Wu (CR46) 2020; 579 Miragaia (CR16) 2019; 50 Priceman (CR38) 2013; 110 Haghverdi, Buettner, Theis (CR56) 2015; 31 Tibbitt (CR32) 2019; 51 La Manno (CR41) 2018; 560 Butler (CR55) 2018; 36 CR48 Muranski (CR59) 2011; 35 Sefik (CR51) 2015; 349 Wei (CR43) 2019; 50 Stoeckius (CR18) 2018; 19 Yosef (CR19) 2013; 496 Cano-Gamez (CR49) 2020; 11 Bodenhofer, Kothmeier, Hochreiter (CR63) 2011; 27 Baron (CR31) 2019; 179 Ghoreschi (CR23) 2010; 467 Yusuf (CR61) 2010; 185 Lee (CR22) 2012; 13 Spits (CR11) 2013; 13 Krausgruber (CR40) 2016; 7 Bottomly (CR2) 1988; 9 Crotty (CR7) 2011; 29 Ciofani (CR58) 2012; 151 Killar (CR4) 1987; 138 Aghaeepour (CR29) 2018; 34 O’Shea, Paul (CR9) 2010; 327 McGeachy (CR39) 2007; 8 Geginat (CR14) 2014; 5 Azizi (CR45) 2018; 174 Camberis, Le, Urban (CR54) 2003; 55 Zeisel (CR64) 2015; 347 van Dijk (CR57) 2018; 174 Li (CR44) 2019; 176 Zhu, Paul (CR10) 2008; 112 Murphy (CR8) 2000; 18 Cosgrove (CR36) 1991; 66 Lee (CR17) 2015; 42 Murphy, Stockinger (CR13) 2010; 11 Hartigan, Hartigan (CR20) 1985; 13 Becht (CR30) 2019; 35 Pavlidis, Hofmeyr, Tasoulis (CR21) 2016; 17 Schep, Wu, Buenrostro, Greenleaf (CR28) 2017; 14 Hess, Ladel, Miko, Kaufmann (CR52) 1996; 156 CR65 Mosmann (CR3) 1986; 136 Buenrostro (CR26) 2015; 523 Nurieva (CR60) 2008; 29 Meredith, Zemmour, Mathis, Benoist (CR25) 2015; 16 Yoshida (CR27) 2019; 176 J Hess (836_CR52) 1996; 156 S Omenetti (836_CR24) 2019; 51 JJ O’Shea (836_CR9) 2010; 327 JW Collins (836_CR53) 2014; 12 H Spits (836_CR11) 2013; 13 JA Hartigan (836_CR20) 1985; 13 CS Baron (836_CR31) 2019; 179 SC Wei (836_CR43) 2019; 50 K Ghoreschi (836_CR23) 2010; 467 836_CR65 M Stoeckius (836_CR34) 2017; 14 RI Nurieva (836_CR60) 2008; 29 N Yosef (836_CR19) 2013; 496 SJ Priceman (836_CR38) 2013; 110 TR Mosmann (836_CR3) 1986; 136 M Meredith (836_CR25) 2015; 16 K Bottomly (836_CR2) 1988; 9 S Crotty (836_CR7) 2011; 29 L Killar (836_CR4) 1987; 138 E Becht (836_CR30) 2019; 35 J Geginat (836_CR14) 2014; 5 RJ Miragaia (836_CR16) 2019; 50 S Becattini (836_CR42) 2015; 347 S Mostafavi (836_CR50) 2016; 164 H Yoshida (836_CR27) 2019; 176 T Krausgruber (836_CR40) 2016; 7 P Muranski (836_CR59) 2011; 35 836_CR35 AN Schep (836_CR28) 2017; 14 R Zilionis (836_CR47) 2019; 50 NG Pavlidis (836_CR21) 2016; 17 E Cano-Gamez (836_CR49) 2020; 11 MS Kowalczyk (836_CR62) 2015; 25 A Kelso (836_CR12) 1995; 16 MJ McGeachy (836_CR39) 2007; 8 H Li (836_CR44) 2019; 176 N Aghaeepour (836_CR29) 2018; 34 A Zeisel (836_CR64) 2015; 347 836_CR48 R Jabeen (836_CR6) 2012; 24 T Korn (836_CR5) 2009; 27 E Sefik (836_CR51) 2015; 349 CA Tibbitt (836_CR32) 2019; 51 L Haghverdi (836_CR56) 2015; 31 U Bodenhofer (836_CR63) 2011; 27 G La Manno (836_CR41) 2018; 560 M Camberis (836_CR54) 2003; 55 D Cosgrove (836_CR36) 1991; 66 BA Araneo (836_CR1) 1975; 114 JY Lee (836_CR17) 2015; 42 J Zhu (836_CR10) 2008; 112 MJT Stubbington (836_CR15) 2017; 358 I Yusuf (836_CR61) 2010; 185 TD Wu (836_CR46) 2020; 579 TB Alexander (836_CR37) 2018; 562 M Ciofani (836_CR58) 2012; 151 Y Lee (836_CR22) 2012; 13 A Butler (836_CR55) 2018; 36 D van Dijk (836_CR57) 2018; 174 JD Buenrostro (836_CR26) 2015; 523 A Arazi (836_CR33) 2019; 20 KM Murphy (836_CR8) 2000; 18 KM Murphy (836_CR13) 2010; 11 M Stoeckius (836_CR18) 2018; 19 E Azizi (836_CR45) 2018; 174 |
| References_xml | – volume: 174 start-page: 1293 year: 2018 end-page: 1308 ident: CR45 article-title: Single-cell map of diverse immune phenotypes in the breast tumor microenvironment publication-title: Cell doi: 10.1016/j.cell.2018.05.060 – volume: 50 start-page: 1084 year: 2019 end-page: 1098 ident: CR43 article-title: Negative co-stimulation constrains T cell differentiation by imposing boundaries on possible cell states publication-title: Immunity doi: 10.1016/j.immuni.2019.03.004 – volume: 16 start-page: 374 year: 1995 end-page: 379 ident: CR12 article-title: T 1 and T 2 subsets: paradigms lost? publication-title: Immunol. Today doi: 10.1016/0167-5699(95)80004-2 – volume: 347 start-page: 400 year: 2015 end-page: 406 ident: CR42 article-title: Functional heterogeneity of human memory CD4 T cell clones primed by pathogens or vaccines publication-title: Science doi: 10.1126/science.1260668 – volume: 496 start-page: 461 year: 2013 end-page: 468 ident: CR19 article-title: Dynamic regulatory network controlling T 17 cell differentiation publication-title: Nature doi: 10.1038/nature11981 – volume: 17 start-page: 5414 year: 2016 end-page: 5446 ident: CR21 article-title: Minimum density hyperplanes publication-title: J. Mach. Learn. Res. – volume: 7 year: 2016 ident: CR40 article-title: T-bet is a key modulator of IL-23-driven pathogenic CD4 T cell responses in the intestine publication-title: Nat. Commun. doi: 10.1038/ncomms11627 – volume: 347 start-page: 1138 year: 2015 end-page: 1142 ident: CR64 article-title: Brain structure. Cell types in the mouse cortex and hippocampus revealed by single-cell RNA-seq publication-title: Science doi: 10.1126/science.aaa1934 – volume: 114 start-page: 747 year: 1975 end-page: 751 ident: CR1 article-title: Functional heterogeneity among the T-derived lymphocytes of the mouse. II. Sensitivity of subpopulations to anti-thymocyte serum publication-title: J. Immunol. doi: 10.4049/jimmunol.114.2_Part_2.747 – ident: CR35 – volume: 138 start-page: 1674 year: 1987 end-page: 1679 ident: CR4 article-title: Cloned, Ia-restricted T cells that do not produce interleukin 4 (IL-4)/B cell stimulatory factor 1 (BSF-1) fail to help antigen-specific B cells publication-title: J. Immunol. doi: 10.4049/jimmunol.138.6.1674 – volume: 523 start-page: 486 year: 2015 end-page: 490 ident: CR26 article-title: Single-cell chromatin accessibility reveals principles of regulatory variation publication-title: Nature doi: 10.1038/nature14590 – volume: 24 start-page: 303 year: 2012 end-page: 307 ident: CR6 article-title: The symphony of the ninth: the development and function of T 9 cells publication-title: Curr. Opin. Immunol. doi: 10.1016/j.coi.2012.02.001 – volume: 55 start-page: 19.12.1 year: 2003 end-page: 19.12.27 ident: CR54 article-title: Animal model of and publication-title: Curr. Protoc. Immunol. – volume: 12 start-page: 612 year: 2014 end-page: 623 ident: CR53 article-title: : infection, inflammation and the microbiota publication-title: Nat. Rev. Microbiol. doi: 10.1038/nrmicro3315 – volume: 14 start-page: 975 year: 2017 end-page: 978 ident: CR28 article-title: chromVAR: inferring transcription-factor-associated accessibility from single-cell epigenomic data publication-title: Nat. Methods doi: 10.1038/nmeth.4401 – volume: 136 start-page: 2348 year: 1986 end-page: 2357 ident: CR3 article-title: Two types of murine helper T cell clone. I. Definition according to profiles of lymphokine activities and secreted proteins publication-title: J. Immunol. doi: 10.4049/jimmunol.136.7.2348 – volume: 13 start-page: 70 year: 1985 end-page: 84 ident: CR20 article-title: The dip test of unimodality publication-title: Ann. Stat. doi: 10.1214/aos/1176346577 – volume: 35 start-page: 301 year: 2019 end-page: 308 ident: CR30 article-title: Reverse-engineering flow-cytometry gating strategies for phenotypic labelling and high-performance cell sorting publication-title: Bioinformatics doi: 10.1093/bioinformatics/bty491 – volume: 467 start-page: 967 year: 2010 end-page: 971 ident: CR23 article-title: Generation of pathogenic T 17 cells in the absence of TGF-β signalling publication-title: Nature doi: 10.1038/nature09447 – volume: 176 start-page: 897 year: 2019 end-page: 912 ident: CR27 article-title: The -regulatory atlas of the mouse immune system publication-title: Cell doi: 10.1016/j.cell.2018.12.036 – volume: 164 start-page: 564 year: 2016 end-page: 578 ident: CR50 article-title: Parsing the interferon transcriptional network and its disease associations publication-title: Cell doi: 10.1016/j.cell.2015.12.032 – volume: 50 start-page: 493 year: 2019 end-page: 504 ident: CR16 article-title: Single-cell transcriptomics of regulatory T cells reveals trajectories of tissue adaptation publication-title: Immunity doi: 10.1016/j.immuni.2019.01.001 – volume: 34 start-page: 4131 year: 2018 end-page: 4133 ident: CR29 article-title: GateFinder: projection-based gating strategy optimization for flow and mass cytometry publication-title: Bioinformatics doi: 10.1093/bioinformatics/bty430 – volume: 50 start-page: 1317 year: 2019 end-page: 1334 ident: CR47 article-title: Single-cell transcriptomics of human and mouse lung cancers reveals conserved myeloid populations across individuals and species publication-title: Immunity doi: 10.1016/j.immuni.2019.03.009 – volume: 13 start-page: 991 year: 2012 end-page: 999 ident: CR22 article-title: Induction and molecular signature of pathogenic T 17 cells publication-title: Nat. Immunol. doi: 10.1038/ni.2416 – volume: 29 start-page: 138 year: 2008 end-page: 149 ident: CR60 article-title: Generation of T follicular helper cells is mediated by interleukin-21 but independent of T helper 1, 2, or 17 cell lineages publication-title: Immunity doi: 10.1016/j.immuni.2008.05.009 – volume: 110 start-page: 13079 year: 2013 end-page: 13084 ident: CR38 article-title: Regulation of adipose tissue T cell subsets by Stat3 is crucial for diet-induced obesity and insulin resistance publication-title: Proc. Natl Acad. Sci. USA doi: 10.1073/pnas.1311557110 – volume: 185 start-page: 190 year: 2010 end-page: 202 ident: CR61 article-title: Germinal center T follicular helper cell IL-4 production is dependent on signaling lymphocytic activation molecule receptor (CD150) publication-title: J. Immunol. doi: 10.4049/jimmunol.0903505 – volume: 27 start-page: 485 year: 2009 end-page: 517 ident: CR5 article-title: IL-17 and T 17 cells publication-title: Annu. Rev. Immunol. doi: 10.1146/annurev.immunol.021908.132710 – volume: 179 start-page: 527 year: 2019 end-page: 542 ident: CR31 article-title: Cell type purification by single-cell transcriptome-trained sorting publication-title: Cell doi: 10.1016/j.cell.2019.08.006 – volume: 174 start-page: 716 year: 2018 end-page: 729 ident: CR57 article-title: Recovering gene interactions from single-cell data using data diffusion publication-title: Cell doi: 10.1016/j.cell.2018.05.061 – volume: 16 start-page: 942 year: 2015 end-page: 949 ident: CR25 article-title: Aire controls gene expression in the thymic epithelium with ordered stochasticity publication-title: Nat. Immunol. doi: 10.1038/ni.3247 – volume: 20 start-page: 902 year: 2019 end-page: 914 ident: CR33 article-title: The immune cell landscape in kidneys of patients with lupus nephritis publication-title: Nat. Immunol. doi: 10.1038/s41590-019-0398-x – volume: 42 start-page: 252 year: 2015 end-page: 264 ident: CR17 article-title: The transcription factor KLF2 restrains CD4 T follicular helper cell differentiation publication-title: Immunity doi: 10.1016/j.immuni.2015.01.013 – volume: 51 start-page: 77 year: 2019 end-page: 89 ident: CR24 article-title: The intestine harbors functionally distinct homeostatic tissue-resident and inflammatory T 17 cells publication-title: Immunity doi: 10.1016/j.immuni.2019.05.004 – volume: 36 start-page: 411 year: 2018 end-page: 420 ident: CR55 article-title: Integrating single-cell transcriptomic data across different conditions, technologies, and species publication-title: Nat. Biotechnol. doi: 10.1038/nbt.4096 – volume: 35 start-page: 972 year: 2011 end-page: 985 ident: CR59 article-title: T 17 cells are long lived and retain a stem cell-like molecular signature publication-title: Immunity doi: 10.1016/j.immuni.2011.09.019 – volume: 18 start-page: 451 year: 2000 end-page: 494 ident: CR8 article-title: Signaling and transcription in T helper development publication-title: Annu. Rev. Immunol. doi: 10.1146/annurev.immunol.18.1.451 – volume: 560 start-page: 494 year: 2018 end-page: 498 ident: CR41 article-title: RNA velocity of single cells publication-title: Nature doi: 10.1038/s41586-018-0414-6 – volume: 13 start-page: 145 year: 2013 end-page: 149 ident: CR11 article-title: Innate lymphoid cells—a proposal for uniform nomenclature publication-title: Nat. Rev. Immunol. doi: 10.1038/nri3365 – volume: 156 start-page: 3321 year: 1996 end-page: 3326 ident: CR52 article-title: infection in gene-targeted immunodeficient mice: major role of CD4 TCR-αβ cells and IFN-γ in bacterial clearance independent of intracellular location publication-title: J. Immunol. doi: 10.4049/jimmunol.156.9.3321 – volume: 31 start-page: 2989 year: 2015 end-page: 2998 ident: CR56 article-title: Diffusion maps for high-dimensional single-cell analysis of differentiation data publication-title: Bioinformatics doi: 10.1093/bioinformatics/btv325 – volume: 579 start-page: 274 year: 2020 end-page: 278 ident: CR46 article-title: Peripheral T cell expansion predicts tumour infiltration and clinical response publication-title: Nature doi: 10.1038/s41586-020-2056-8 – volume: 25 start-page: 1860 year: 2015 end-page: 1872 ident: CR62 article-title: Single-cell RNA-seq reveals changes in cell cycle and differentiation programs upon aging of hematopoietic stem cells publication-title: Genome Res. doi: 10.1101/gr.192237.115 – volume: 27 start-page: 2463 year: 2011 end-page: 2464 ident: CR63 article-title: APCluster: an R package for affinity propagation clustering publication-title: Bioinformatics doi: 10.1093/bioinformatics/btr406 – volume: 66 start-page: 1051 year: 1991 end-page: 1066 ident: CR36 article-title: Mice lacking MHC class II molecules publication-title: Cell doi: 10.1016/0092-8674(91)90448-8 – volume: 11 year: 2020 ident: CR49 article-title: Single-cell transcriptomics identifies an effectorness gradient shaping the response of CD4 T cells to cytokines publication-title: Nat. Commun. doi: 10.1038/s41467-020-15543-y – ident: CR48 – volume: 19 year: 2018 ident: CR18 article-title: Cell hashing with barcoded antibodies enables multiplexing and doublet detection for single cell genomics publication-title: Genome Biol. doi: 10.1186/s13059-018-1603-1 – ident: CR65 – volume: 14 start-page: 865 year: 2017 end-page: 868 ident: CR34 article-title: Simultaneous epitope and transcriptome measurement in single cells publication-title: Nat. Methods doi: 10.1038/nmeth.4380 – volume: 349 start-page: 993 year: 2015 end-page: 997 ident: CR51 article-title: Individual intestinal symbionts induce a distinct population of RORγ regulatory T cells publication-title: Science doi: 10.1126/science.aaa9420 – volume: 29 start-page: 621 year: 2011 end-page: 663 ident: CR7 article-title: Follicular helper CD4 T cells (T ) publication-title: Annu. Rev. Immunol. doi: 10.1146/annurev-immunol-031210-101400 – volume: 327 start-page: 1098 year: 2010 end-page: 1102 ident: CR9 article-title: Mechanisms underlying lineage commitment and plasticity of helper CD4 T cells publication-title: Science doi: 10.1126/science.1178334 – volume: 11 start-page: 674 year: 2010 end-page: 680 ident: CR13 article-title: Effector T cell plasticity: flexibility in the face of changing circumstances publication-title: Nat. Immunol. doi: 10.1038/ni.1899 – volume: 112 start-page: 1557 year: 2008 end-page: 1569 ident: CR10 article-title: CD4 T cells: fates, functions, and faults publication-title: Blood doi: 10.1182/blood-2008-05-078154 – volume: 5 start-page: 630 year: 2014 ident: CR14 article-title: Plasticity of human CD4 T cell subsets publication-title: Front. Immunol. doi: 10.3389/fimmu.2014.00630 – volume: 8 start-page: 1390 year: 2007 end-page: 1397 ident: CR39 article-title: TGF-β and IL-6 drive the production of IL-17 and IL-10 by T cells and restrain T -17 cell-mediated pathology publication-title: Nat. Immunol. doi: 10.1038/ni1539 – volume: 562 start-page: 373 year: 2018 end-page: 379 ident: CR37 article-title: The genetic basis and cell of origin of mixed phenotype acute leukaemia publication-title: Nature doi: 10.1038/s41586-018-0436-0 – volume: 9 start-page: 268 year: 1988 end-page: 274 ident: CR2 article-title: A functional dichotomy in CD4 T lymphocytes publication-title: Immunol. Today doi: 10.1016/0167-5699(88)91308-4 – volume: 151 start-page: 289 year: 2012 end-page: 303 ident: CR58 article-title: A validated regulatory network for T 17 cell specification publication-title: Cell doi: 10.1016/j.cell.2012.09.016 – volume: 176 start-page: 775 year: 2019 end-page: 789 ident: CR44 article-title: Dysfunctional CD8 T cells form a proliferative, dynamically regulated compartment within human melanoma publication-title: Cell doi: 10.1016/j.cell.2018.11.043 – volume: 358 start-page: 58 year: 2017 end-page: 63 ident: CR15 article-title: Single-cell transcriptomics to explore the immune system in health and disease publication-title: Science doi: 10.1126/science.aan6828 – volume: 51 start-page: 169 year: 2019 end-page: 184 ident: CR32 article-title: Single-cell RNA sequencing of the T helper cell response to house dust mites defines a distinct gene expression signature in airway T 2 cells publication-title: Immunity doi: 10.1016/j.immuni.2019.05.014 – volume: 7 year: 2016 ident: 836_CR40 publication-title: Nat. Commun. doi: 10.1038/ncomms11627 – volume: 50 start-page: 493 year: 2019 ident: 836_CR16 publication-title: Immunity doi: 10.1016/j.immuni.2019.01.001 – volume: 467 start-page: 967 year: 2010 ident: 836_CR23 publication-title: Nature doi: 10.1038/nature09447 – volume: 560 start-page: 494 year: 2018 ident: 836_CR41 publication-title: Nature doi: 10.1038/s41586-018-0414-6 – volume: 50 start-page: 1317 year: 2019 ident: 836_CR47 publication-title: Immunity doi: 10.1016/j.immuni.2019.03.009 – volume: 16 start-page: 374 year: 1995 ident: 836_CR12 publication-title: Immunol. Today doi: 10.1016/0167-5699(95)80004-2 – volume: 174 start-page: 1293 year: 2018 ident: 836_CR45 publication-title: Cell doi: 10.1016/j.cell.2018.05.060 – volume: 51 start-page: 169 year: 2019 ident: 836_CR32 publication-title: Immunity doi: 10.1016/j.immuni.2019.05.014 – volume: 349 start-page: 993 year: 2015 ident: 836_CR51 publication-title: Science doi: 10.1126/science.aaa9420 – volume: 18 start-page: 451 year: 2000 ident: 836_CR8 publication-title: Annu. Rev. Immunol. doi: 10.1146/annurev.immunol.18.1.451 – volume: 327 start-page: 1098 year: 2010 ident: 836_CR9 publication-title: Science doi: 10.1126/science.1178334 – ident: 836_CR48 doi: 10.1101/461228 – volume: 13 start-page: 70 year: 1985 ident: 836_CR20 publication-title: Ann. Stat. doi: 10.1214/aos/1176346577 – volume: 16 start-page: 942 year: 2015 ident: 836_CR25 publication-title: Nat. Immunol. doi: 10.1038/ni.3247 – volume: 496 start-page: 461 year: 2013 ident: 836_CR19 publication-title: Nature doi: 10.1038/nature11981 – volume: 17 start-page: 5414 year: 2016 ident: 836_CR21 publication-title: J. Mach. Learn. Res. – volume: 27 start-page: 485 year: 2009 ident: 836_CR5 publication-title: Annu. Rev. Immunol. doi: 10.1146/annurev.immunol.021908.132710 – volume: 112 start-page: 1557 year: 2008 ident: 836_CR10 publication-title: Blood doi: 10.1182/blood-2008-05-078154 – volume: 8 start-page: 1390 year: 2007 ident: 836_CR39 publication-title: Nat. Immunol. doi: 10.1038/ni1539 – volume: 50 start-page: 1084 year: 2019 ident: 836_CR43 publication-title: Immunity doi: 10.1016/j.immuni.2019.03.004 – volume: 19 year: 2018 ident: 836_CR18 publication-title: Genome Biol. doi: 10.1186/s13059-018-1603-1 – volume: 562 start-page: 373 year: 2018 ident: 836_CR37 publication-title: Nature doi: 10.1038/s41586-018-0436-0 – volume: 185 start-page: 190 year: 2010 ident: 836_CR61 publication-title: J. Immunol. doi: 10.4049/jimmunol.0903505 – volume: 42 start-page: 252 year: 2015 ident: 836_CR17 publication-title: Immunity doi: 10.1016/j.immuni.2015.01.013 – volume: 176 start-page: 897 year: 2019 ident: 836_CR27 publication-title: Cell doi: 10.1016/j.cell.2018.12.036 – volume: 29 start-page: 138 year: 2008 ident: 836_CR60 publication-title: Immunity doi: 10.1016/j.immuni.2008.05.009 – volume: 5 start-page: 630 year: 2014 ident: 836_CR14 publication-title: Front. Immunol. doi: 10.3389/fimmu.2014.00630 – volume: 31 start-page: 2989 year: 2015 ident: 836_CR56 publication-title: Bioinformatics doi: 10.1093/bioinformatics/btv325 – volume: 14 start-page: 975 year: 2017 ident: 836_CR28 publication-title: Nat. Methods doi: 10.1038/nmeth.4401 – volume: 138 start-page: 1674 year: 1987 ident: 836_CR4 publication-title: J. Immunol. doi: 10.4049/jimmunol.138.6.1674 – volume: 358 start-page: 58 year: 2017 ident: 836_CR15 publication-title: Science doi: 10.1126/science.aan6828 – volume: 51 start-page: 77 year: 2019 ident: 836_CR24 publication-title: Immunity doi: 10.1016/j.immuni.2019.05.004 – volume: 176 start-page: 775 year: 2019 ident: 836_CR44 publication-title: Cell doi: 10.1016/j.cell.2018.11.043 – volume: 14 start-page: 865 year: 2017 ident: 836_CR34 publication-title: Nat. Methods doi: 10.1038/nmeth.4380 – volume: 27 start-page: 2463 year: 2011 ident: 836_CR63 publication-title: Bioinformatics doi: 10.1093/bioinformatics/btr406 – volume: 34 start-page: 4131 year: 2018 ident: 836_CR29 publication-title: Bioinformatics doi: 10.1093/bioinformatics/bty430 – volume: 20 start-page: 902 year: 2019 ident: 836_CR33 publication-title: Nat. Immunol. doi: 10.1038/s41590-019-0398-x – volume: 66 start-page: 1051 year: 1991 ident: 836_CR36 publication-title: Cell doi: 10.1016/0092-8674(91)90448-8 – volume: 523 start-page: 486 year: 2015 ident: 836_CR26 publication-title: Nature doi: 10.1038/nature14590 – volume: 11 year: 2020 ident: 836_CR49 publication-title: Nat. Commun. doi: 10.1038/s41467-020-15543-y – volume: 55 start-page: 19.12.1 year: 2003 ident: 836_CR54 publication-title: Curr. Protoc. Immunol. doi: 10.1002/0471142735.im1912s55 – volume: 151 start-page: 289 year: 2012 ident: 836_CR58 publication-title: Cell doi: 10.1016/j.cell.2012.09.016 – volume: 13 start-page: 991 year: 2012 ident: 836_CR22 publication-title: Nat. Immunol. doi: 10.1038/ni.2416 – volume: 347 start-page: 400 year: 2015 ident: 836_CR42 publication-title: Science doi: 10.1126/science.1260668 – volume: 35 start-page: 972 year: 2011 ident: 836_CR59 publication-title: Immunity doi: 10.1016/j.immuni.2011.09.019 – volume: 24 start-page: 303 year: 2012 ident: 836_CR6 publication-title: Curr. Opin. Immunol. doi: 10.1016/j.coi.2012.02.001 – volume: 35 start-page: 301 year: 2019 ident: 836_CR30 publication-title: Bioinformatics doi: 10.1093/bioinformatics/bty491 – volume: 11 start-page: 674 year: 2010 ident: 836_CR13 publication-title: Nat. Immunol. doi: 10.1038/ni.1899 – volume: 114 start-page: 747 year: 1975 ident: 836_CR1 publication-title: J. Immunol. doi: 10.4049/jimmunol.114.2_Part_2.747 – volume: 136 start-page: 2348 year: 1986 ident: 836_CR3 publication-title: J. Immunol. doi: 10.4049/jimmunol.136.7.2348 – ident: 836_CR65 doi: 10.1101/2020.01.23.911966 – volume: 36 start-page: 411 year: 2018 ident: 836_CR55 publication-title: Nat. Biotechnol. doi: 10.1038/nbt.4096 – volume: 25 start-page: 1860 year: 2015 ident: 836_CR62 publication-title: Genome Res. doi: 10.1101/gr.192237.115 – volume: 174 start-page: 716 year: 2018 ident: 836_CR57 publication-title: Cell doi: 10.1016/j.cell.2018.05.061 – volume: 579 start-page: 274 year: 2020 ident: 836_CR46 publication-title: Nature doi: 10.1038/s41586-020-2056-8 – ident: 836_CR35 doi: 10.1002/cyto.a.24027 – volume: 110 start-page: 13079 year: 2013 ident: 836_CR38 publication-title: Proc. Natl Acad. Sci. USA doi: 10.1073/pnas.1311557110 – volume: 13 start-page: 145 year: 2013 ident: 836_CR11 publication-title: Nat. Rev. Immunol. doi: 10.1038/nri3365 – volume: 179 start-page: 527 year: 2019 ident: 836_CR31 publication-title: Cell doi: 10.1016/j.cell.2019.08.006 – volume: 9 start-page: 268 year: 1988 ident: 836_CR2 publication-title: Immunol. Today doi: 10.1016/0167-5699(88)91308-4 – volume: 156 start-page: 3321 year: 1996 ident: 836_CR52 publication-title: J. Immunol. doi: 10.4049/jimmunol.156.9.3321 – volume: 29 start-page: 621 year: 2011 ident: 836_CR7 publication-title: Annu. Rev. Immunol. doi: 10.1146/annurev-immunol-031210-101400 – volume: 164 start-page: 564 year: 2016 ident: 836_CR50 publication-title: Cell doi: 10.1016/j.cell.2015.12.032 – volume: 347 start-page: 1138 year: 2015 ident: 836_CR64 publication-title: Science doi: 10.1126/science.aaa1934 – volume: 12 start-page: 612 year: 2014 ident: 836_CR53 publication-title: Nat. Rev. Microbiol. doi: 10.1038/nrmicro3315 |
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| Snippet | CD4
+
effector lymphocytes (T
eff
) are traditionally classified by the cytokines they produce. To determine the states that T
eff
cells actually adopt in... CD4+ effector lymphocytes (Teff) are traditionally classified by the cytokines they produce. To determine the states that Teff cells actually adopt in... CD4 + effector lymphocytes (Teff) are traditionally classified by the cytokines they produce. To determine the states that Teff actually adopt in frontline... |
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| SubjectTerms | 631/250 631/250/2152 631/337 Biomedical and Life Sciences Biomedicine CD4 antigen Chromatin Cytokines GATA-3 protein Gene expression Germfree Immunology Infectious Diseases Lymphocytes Lymphocytes T Microorganisms Phenotypes Transcriptomes γ-Interferon |
| Title | Gut CD4+ T cell phenotypes are a continuum molded by microbes, not by TH archetypes |
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