Epithelial endoplasmic reticulum stress orchestrates a protective IgA response
Immunoglobulin A (IgA) is the major secretory immunoglobulin isotype found at mucosal surfaces, where it regulates microbial commensalism and excludes luminal factors from contacting intestinal epithelial cells (IECs). IgA is induced by both T cell–dependent and –independent (TI) pathways. However,...
Saved in:
| Published in | Science (American Association for the Advancement of Science) Vol. 363; no. 6430; pp. 993 - 998 |
|---|---|
| Main Authors | , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , |
| Format | Journal Article |
| Language | English |
| Published |
United States
American Association for the Advancement of Science
01.03.2019
The American Association for the Advancement of Science |
| Subjects | |
| Online Access | Get full text |
Cover
Loading…
| Abstract | Immunoglobulin A (IgA) is the major secretory immunoglobulin isotype found at mucosal surfaces, where it regulates microbial commensalism and excludes luminal factors from contacting intestinal epithelial cells (IECs). IgA is induced by both T cell–dependent and –independent (TI) pathways. However, little is known about TI regulation. We report that IEC endoplasmic reticulum (ER) stress induces a polyreactive IgA response, which is protective against enteric inflammation. IEC ER stress causes TI and microbiota-independent expansion and activation of peritoneal B1b cells, which culminates in increased lamina propria and luminal IgA. Increased numbers of IgA-producing plasma cells were observed in healthy humans with defective autophagy, who are known to exhibit IEC ER stress. Upon ER stress, IECs communicate signals to the peritoneum that induce a barrier-protective TI IgA response. |
|---|---|
| AbstractList | Immunoglobulin A (IgA) is the major secretory immunoglobulin isotype found at mucosal surfaces, where it regulates microbial commensalism and excludes luminal factors from contacting intestinal epithelial cells (IECs). IgA is induced by both T cell-dependent and -independent (TI) pathways. However, little is known about TI regulation. We report that IEC endoplasmic reticulum (ER) stress induces a polyreactive IgA response, which is protective against enteric inflammation. IEC ER stress causes TI and microbiota-independent expansion and activation of peritoneal B1b cells, which culminates in increased lamina propria and luminal IgA. Increased numbers of IgA-producing plasma cells were observed in healthy humans with defective autophagy, who are known to exhibit IEC ER stress. Upon ER stress, IECs communicate signals to the peritoneum that induce a barrier-protective TI IgA response.Immunoglobulin A (IgA) is the major secretory immunoglobulin isotype found at mucosal surfaces, where it regulates microbial commensalism and excludes luminal factors from contacting intestinal epithelial cells (IECs). IgA is induced by both T cell-dependent and -independent (TI) pathways. However, little is known about TI regulation. We report that IEC endoplasmic reticulum (ER) stress induces a polyreactive IgA response, which is protective against enteric inflammation. IEC ER stress causes TI and microbiota-independent expansion and activation of peritoneal B1b cells, which culminates in increased lamina propria and luminal IgA. Increased numbers of IgA-producing plasma cells were observed in healthy humans with defective autophagy, who are known to exhibit IEC ER stress. Upon ER stress, IECs communicate signals to the peritoneum that induce a barrier-protective TI IgA response. Immunoglobulin A (IgA) is the most abundantly expressed antibody isotype and can be found at various mucosal surfaces in the body, including the gastrointestinal (GI) tract. IgA is polyreactive and can coat and restrain both commensal bacteria and enteric pathogens. Grootjans et al. found that endoplasmic reticulum (ER) stress in the intestinal epithelial cells of mice induced the T cell– and microbiota-independent expansion of peritoneal B1b cells, which secrete IgA. Similarly, human subjects homozygous for a variant of an autophagy gene ( ATG16L1 ) known to cause ER stress showed increased numbers of GI IgA + cells compared with controls. Thus, epithelial ER stress serves as an advantageous “eustress” response that can functionally antagonize its well-characterized role in promoting inflammation. Science , this issue p. 993 Gut epithelial endoplasmic reticulum stress induces barrier-protective immunoglobulin A secretion in mice. Immunoglobulin A (IgA) is the major secretory immunoglobulin isotype found at mucosal surfaces, where it regulates microbial commensalism and excludes luminal factors from contacting intestinal epithelial cells (IECs). IgA is induced by both T cell–dependent and –independent (TI) pathways. However, little is known about TI regulation. We report that IEC endoplasmic reticulum (ER) stress induces a polyreactive IgA response, which is protective against enteric inflammation. IEC ER stress causes TI and microbiota-independent expansion and activation of peritoneal B1b cells, which culminates in increased lamina propria and luminal IgA. Increased numbers of IgA-producing plasma cells were observed in healthy humans with defective autophagy, who are known to exhibit IEC ER stress. Upon ER stress, IECs communicate signals to the peritoneum that induce a barrier-protective TI IgA response. Stressed gut epithelium gets some reliefImmunoglobulin A (IgA) is the most abundantly expressed antibody isotype and can be found at various mucosal surfaces in the body, including the gastrointestinal (GI) tract. IgA is polyreactive and can coat and restrain both commensal bacteria and enteric pathogens. Grootjans et al. found that endoplasmic reticulum (ER) stress in the intestinal epithelial cells of mice induced the T cell– and microbiota-independent expansion of peritoneal B1b cells, which secrete IgA. Similarly, human subjects homozygous for a variant of an autophagy gene (ATG16L1) known to cause ER stress showed increased numbers of GI IgA+ cells compared with controls. Thus, epithelial ER stress serves as an advantageous “eustress” response that can functionally antagonize its well-characterized role in promoting inflammation.Science, this issue p. 993Immunoglobulin A (IgA) is the major secretory immunoglobulin isotype found at mucosal surfaces, where it regulates microbial commensalism and excludes luminal factors from contacting intestinal epithelial cells (IECs). IgA is induced by both T cell–dependent and –independent (TI) pathways. However, little is known about TI regulation. We report that IEC endoplasmic reticulum (ER) stress induces a polyreactive IgA response, which is protective against enteric inflammation. IEC ER stress causes TI and microbiota-independent expansion and activation of peritoneal B1b cells, which culminates in increased lamina propria and luminal IgA. Increased numbers of IgA-producing plasma cells were observed in healthy humans with defective autophagy, who are known to exhibit IEC ER stress. Upon ER stress, IECs communicate signals to the peritoneum that induce a barrier-protective TI IgA response. Immunoglobulin A (IgA) is the major secretory immunoglobulin isotype found at mucosal surfaces, where it regulates microbial commensalism and excludes luminal factors from contacting intestinal epithelial cells (IECs). IgA is induced by both T cell-dependent and -independent (TI) pathways. However, little is known about TI regulation. We report that IEC endoplasmic reticulum (ER) stress induces a polyreactive IgA response, which is protective against enteric inflammation. IEC ER stress causes TI and microbiota-independent expansion and activation of peritoneal B1b cells, which culminates in increased lamina propria and luminal IgA. Increased numbers of IgA-producing plasma cells were observed in healthy humans with defective autophagy, who are known to exhibit IEC ER stress. Upon ER stress, IECs communicate signals to the peritoneum that induce a barrier-protective TI IgA response. |
| Author | Matute, Juan D. Glickman, Jonathan N. Kaser, Arthur Targan, Stephan R. Ganal-Vonarburg, Stephanie C. Palm, Noah W. Hanley, Thomas Duan, Jinzhi van der Woude, C. Janneke Wucherpfennig, Kai W. Macpherson, Andrew J. Rosenstiel, Philip Saveljeva, Svetlana Blumberg, Richard S. Krupka, Niklas Fuhler, Gwenny M. Heijmans, Jarom Shih, David Q. Luoma, Adrienne M. Limenitakis, Julien P. Flavell, Richard A. Suo, Shengbao de Zoete, Marcel R. Yuan, Guo-Cheng Hosomi, Shuhei McCoy, Kathy D. Shimodaira, Yosuke Conner, Margaret E. Gensollen, Thomas Li, Hai Grootjans, Joep |
| AuthorAffiliation | 5 Division of Neonatology, Department of Pediatrics, Massachusetts General Hospital, Harvard Medical School, Boston, MA 02114, USA 6 Division of Gastroenterology and Hepatology, Department of Medicine, University of Cambridge, Cambridge CB2 0QQ, UK 15 Department of Infectious Diseases and Immunology, Faculty of Veterinary Medicine, Utrecht University, Utrecht, Netherlands 9 Department of Cancer Immunology and Virology, Dana-Farber Cancer Institute, 450 Brookline Avenue, Boston, MA 02215, USA 8 Department of Biostatistics and Computational Biology, Dana-Farber Cancer Institute, Boston, MA 02215, USA 16 Institute of Clinical Molecular Biology, Christian-Albrechts-University Kiel, Rosalind-Franklin-Str. 12, 24105 Kiel, Germany 7 Amsterdam University Medical Center, University of Amsterdam, Department of Internal Medicine, Tygat Institute for Liver and Intestinal Research, Meibergdreef 9, Amsterdam, Netherlands 11 Department of Molecular Virology and Microbiology, Baylor College of Medicine, Hous |
| AuthorAffiliation_xml | – name: 7 Amsterdam University Medical Center, University of Amsterdam, Department of Internal Medicine, Tygat Institute for Liver and Intestinal Research, Meibergdreef 9, Amsterdam, Netherlands – name: 18 Department of Physiology and Pharmacology, University of Calgary, Calgary, Alberta, Canada – name: 8 Department of Biostatistics and Computational Biology, Dana-Farber Cancer Institute, Boston, MA 02215, USA – name: 2 Amsterdam University Medical Center, University of Amsterdam, Department of Gastroenterology and Hepatology and Tygat Institute for Liver and Intestinal Research, Meibergdreef 9, Amsterdam, Netherlands – name: 15 Department of Infectious Diseases and Immunology, Faculty of Veterinary Medicine, Utrecht University, Utrecht, Netherlands – name: 1 Division of Gastroenterology, Department of Medicine, Brigham and Women’s Hospital, Harvard Medical School, 75 Francis Street, Boston, MA 02115, USA – name: 10 F. Widjaja Foundation, Inflammatory Bowel and Immunobiology Research Institute, Cedars-Sinai Medical Center, Los Angeles, CA 90048, USA – name: 11 Department of Molecular Virology and Microbiology, Baylor College of Medicine, Houston, TX 77030, USA – name: 9 Department of Cancer Immunology and Virology, Dana-Farber Cancer Institute, 450 Brookline Avenue, Boston, MA 02215, USA – name: 13 Department of Gastroenterology and Hepatology, Erasmus MC, University Medical Center, Rotterdam, Netherlands – name: 3 Maurice Müller Laboratories (DBMR), Universitätsklinik für Viszerale Chirurgie und Medizin Inselspital, Murtenstrasse 35, University of Bern, 3010 Bern, Switzerland – name: 4 Department of Gastroenterology, Osaka City University Graduate School of Medicine, 1-4-3, Asahi-machi, Abeno-ku, Osaka 545-8585, Japan – name: 14 Department of Immunobiology, Yale University School of Medicine, New Haven, CT 06519, USA – name: 16 Institute of Clinical Molecular Biology, Christian-Albrechts-University Kiel, Rosalind-Franklin-Str. 12, 24105 Kiel, Germany – name: 5 Division of Neonatology, Department of Pediatrics, Massachusetts General Hospital, Harvard Medical School, Boston, MA 02114, USA – name: 6 Division of Gastroenterology and Hepatology, Department of Medicine, University of Cambridge, Cambridge CB2 0QQ, UK – name: 17 Howard Hughes Medical Institute, Yale University School of Medicine, New Haven, CT 06519, USA – name: 12 Department of Pathology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA 02215, USA |
| Author_xml | – sequence: 1 givenname: Joep surname: Grootjans fullname: Grootjans, Joep – sequence: 2 givenname: Niklas surname: Krupka fullname: Krupka, Niklas – sequence: 3 givenname: Shuhei surname: Hosomi fullname: Hosomi, Shuhei – sequence: 4 givenname: Juan D. surname: Matute fullname: Matute, Juan D. – sequence: 5 givenname: Thomas surname: Hanley fullname: Hanley, Thomas – sequence: 6 givenname: Svetlana surname: Saveljeva fullname: Saveljeva, Svetlana – sequence: 7 givenname: Thomas surname: Gensollen fullname: Gensollen, Thomas – sequence: 8 givenname: Jarom surname: Heijmans fullname: Heijmans, Jarom – sequence: 9 givenname: Hai surname: Li fullname: Li, Hai – sequence: 10 givenname: Julien P. surname: Limenitakis fullname: Limenitakis, Julien P. – sequence: 11 givenname: Stephanie C. surname: Ganal-Vonarburg fullname: Ganal-Vonarburg, Stephanie C. – sequence: 12 givenname: Shengbao surname: Suo fullname: Suo, Shengbao – sequence: 13 givenname: Adrienne M. surname: Luoma fullname: Luoma, Adrienne M. – sequence: 14 givenname: Yosuke surname: Shimodaira fullname: Shimodaira, Yosuke – sequence: 15 givenname: Jinzhi surname: Duan fullname: Duan, Jinzhi – sequence: 16 givenname: David Q. surname: Shih fullname: Shih, David Q. – sequence: 17 givenname: Margaret E. surname: Conner fullname: Conner, Margaret E. – sequence: 18 givenname: Jonathan N. surname: Glickman fullname: Glickman, Jonathan N. – sequence: 19 givenname: Gwenny M. surname: Fuhler fullname: Fuhler, Gwenny M. – sequence: 20 givenname: Noah W. surname: Palm fullname: Palm, Noah W. – sequence: 21 givenname: Marcel R. surname: de Zoete fullname: de Zoete, Marcel R. – sequence: 22 givenname: C. Janneke surname: van der Woude fullname: van der Woude, C. Janneke – sequence: 23 givenname: Guo-Cheng surname: Yuan fullname: Yuan, Guo-Cheng – sequence: 24 givenname: Kai W. surname: Wucherpfennig fullname: Wucherpfennig, Kai W. – sequence: 25 givenname: Stephan R. surname: Targan fullname: Targan, Stephan R. – sequence: 26 givenname: Philip surname: Rosenstiel fullname: Rosenstiel, Philip – sequence: 27 givenname: Richard A. surname: Flavell fullname: Flavell, Richard A. – sequence: 28 givenname: Kathy D. surname: McCoy fullname: McCoy, Kathy D. – sequence: 29 givenname: Andrew J. surname: Macpherson fullname: Macpherson, Andrew J. – sequence: 30 givenname: Arthur surname: Kaser fullname: Kaser, Arthur – sequence: 31 givenname: Richard S. surname: Blumberg fullname: Blumberg, Richard S. |
| BackLink | https://www.ncbi.nlm.nih.gov/pubmed/30819965$$D View this record in MEDLINE/PubMed |
| BookMark | eNp9kU1v1DAQhi1U1G5Lz5xAkXrhknYcJ_64IFVVgUoVXOBseZ1J1ysnDrZTiX-P211W0AMn2zPP-86M55QcTWFCQt5SuKS04VfJOpwsXhqTBZX8FVlRUF2tGmBHZAXAeC1BdCfkNKUtQMkpdkxOGEiqFO9W5Ovt7PIGvTO-wqkPszdpdLaKmJ1d_DJWKUdMqQrRbrDcTcZUmWqOIaPN7hGru4frgqc5TAnfkNeD8QnP9-cZ-fHp9vvNl_r-2-e7m-v72rbQ5JpzRgcDUjBT3rLvW2UNk4bKvgRwaKWCfg0CBil6BNUM3doOa0GhlaZvkJ2RjzvfeVmP2FucSmdez9GNJv7SwTj9b2ZyG_0QHnWpLBQXxeDD3iCGn0sZTI8uWfTeTBiWpBsqRUc7xrqCXrxAt2GJUxnvmaJUSgqFev93R4dW_nx1Aa52gI0hpYjDAaGgn5ap98vU-2UWRfdCYV022YWnkZz_j-7dTrdNOcRDmYZzSnmr2G-0nbJM |
| CitedBy_id | crossref_primary_10_1136_egastro_2024_100129 crossref_primary_10_1172_jci_insight_135718 crossref_primary_10_1038_s41577_019_0268_7 crossref_primary_10_1080_14397595_2019_1651446 crossref_primary_10_1038_s41577_021_00506_1 crossref_primary_10_1038_s41392_019_0074_5 crossref_primary_10_3390_cells10123603 crossref_primary_10_3389_fmicb_2022_875238 crossref_primary_10_1016_j_immuni_2019_03_019 crossref_primary_10_1016_j_tim_2023_04_001 crossref_primary_10_1073_pnas_2015080118 crossref_primary_10_1016_j_jcmgh_2024_101423 crossref_primary_10_1016_j_rvsc_2021_04_027 crossref_primary_10_1038_s41416_021_01562_z crossref_primary_10_1016_j_semcancer_2019_11_007 crossref_primary_10_1016_j_immuni_2023_02_018 crossref_primary_10_3389_fmicb_2024_1335036 crossref_primary_10_1016_j_immuni_2019_07_010 crossref_primary_10_3390_molecules24203632 crossref_primary_10_1136_gutjnl_2020_322873 crossref_primary_10_1038_s41418_019_0481_8 crossref_primary_10_1111_imr_13424 crossref_primary_10_1038_s41579_025_01163_0 crossref_primary_10_1111_acer_14220 crossref_primary_10_3390_microorganisms9102117 crossref_primary_10_3390_nano10122460 crossref_primary_10_1126_science_adj1240 crossref_primary_10_1021_acs_jafc_3c00798 crossref_primary_10_1002_jcp_30603 crossref_primary_10_1146_annurev_immunol_082019_081656 crossref_primary_10_1038_s41586_020_2025_2 crossref_primary_10_1002_cti2_1233 crossref_primary_10_1016_j_tcb_2021_01_003 crossref_primary_10_1084_jem_20211938 crossref_primary_10_1016_j_ebiom_2020_102974 crossref_primary_10_1038_s41577_019_0261_1 crossref_primary_10_3390_ijms22052623 crossref_primary_10_1016_j_mib_2020_08_003 crossref_primary_10_1016_j_mucimm_2024_02_008 crossref_primary_10_1016_j_yexcr_2023_113472 crossref_primary_10_1016_j_vetmic_2024_110013 crossref_primary_10_1016_j_lfs_2023_121902 crossref_primary_10_1016_j_biopha_2021_111479 crossref_primary_10_1146_annurev_immunol_093019_112348 crossref_primary_10_1016_j_tox_2021_152799 crossref_primary_10_1093_ecco_jcc_jjz194 crossref_primary_10_1038_s41419_021_04494_x crossref_primary_10_3389_fimmu_2019_02825 crossref_primary_10_4110_in_2020_20_e44 |
| Cites_doi | 10.3791/1488 10.1084/jem.190.7.915 10.1007/BF00917328 10.1111/imr.12189 10.1016/j.cell.2016.04.055 10.3791/50556 10.1038/mi.2017.22 10.1038/nri2322 10.1093/nar/27.1.209 10.1053/j.gastro.2011.05.033 10.1172/JCI85113 10.1186/s12865-014-0040-5 10.1128/MCB.00779-06 10.1053/j.gastro.2013.01.023 10.1038/cr.2008.312 10.1038/nature12599 10.1038/nri3322 10.1016/j.immuni.2015.08.007 10.1084/jem.20160791 10.1126/science.288.5474.2222 10.1006/meth.2001.1262 10.1186/s13059-014-0550-8 10.1038/nbt.4096 10.1093/intimm/11.5.643 10.1126/science.aan6619 10.1016/j.cell.2008.07.021 10.1073/pnas.1315792111 10.4049/jimmunol.162.5.2521 10.1093/bioinformatics/bts635 10.1053/gast.2001.20912 10.1016/j.immuni.2017.06.013 10.1093/bioinformatics/btr260 10.1371/journal.pcbi.1004503 10.1038/mi.2007.6 10.1038/nprot.2016.091 10.1038/nri2901 10.1016/j.cell.2014.08.006 10.1126/scitranslmed.aan1217 10.1016/S1074-7613(01)00088-7 10.1371/journal.pone.0025589 10.1126/science.1086907 10.1073/pnas.0506580102 10.1038/nri.2016.62 10.1136/gutjnl-2012-303527 10.1016/j.cels.2015.12.004 10.1038/nmeth.3364 10.1002/gene.20042 |
| ContentType | Journal Article |
| Copyright | Copyright © 2019 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works. Copyright © 2019 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works |
| Copyright_xml | – notice: Copyright © 2019 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works. – notice: Copyright © 2019 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works |
| DBID | AAYXX CITATION CGR CUY CVF ECM EIF NPM 7QF 7QG 7QL 7QP 7QQ 7QR 7SC 7SE 7SN 7SP 7SR 7SS 7T7 7TA 7TB 7TK 7TM 7U5 7U9 8BQ 8FD C1K F28 FR3 H8D H8G H94 JG9 JQ2 K9. KR7 L7M L~C L~D M7N P64 RC3 7X8 5PM |
| DOI | 10.1126/science.aat7186 |
| DatabaseName | CrossRef Medline MEDLINE MEDLINE (Ovid) MEDLINE MEDLINE PubMed Aluminium Industry Abstracts Animal Behavior Abstracts Bacteriology Abstracts (Microbiology B) Calcium & Calcified Tissue Abstracts Ceramic Abstracts Chemoreception Abstracts Computer and Information Systems Abstracts Corrosion Abstracts Ecology Abstracts Electronics & Communications Abstracts Engineered Materials Abstracts Entomology Abstracts (Full archive) Industrial and Applied Microbiology Abstracts (Microbiology A) Materials Business File Mechanical & Transportation Engineering Abstracts Neurosciences Abstracts Nucleic Acids Abstracts Solid State and Superconductivity Abstracts Virology and AIDS Abstracts METADEX Technology Research Database Environmental Sciences and Pollution Management ANTE: Abstracts in New Technology & Engineering Engineering Research Database Aerospace Database Copper Technical Reference Library AIDS and Cancer Research Abstracts Materials Research Database ProQuest Computer Science Collection ProQuest Health & Medical Complete (Alumni) Civil Engineering Abstracts Advanced Technologies Database with Aerospace Computer and Information Systems Abstracts Academic Computer and Information Systems Abstracts Professional Algology Mycology and Protozoology Abstracts (Microbiology C) Biotechnology and BioEngineering Abstracts Genetics Abstracts MEDLINE - Academic PubMed Central (Full Participant titles) |
| DatabaseTitle | CrossRef MEDLINE Medline Complete MEDLINE with Full Text PubMed MEDLINE (Ovid) Materials Research Database Technology Research Database Computer and Information Systems Abstracts – Academic Mechanical & Transportation Engineering Abstracts Nucleic Acids Abstracts ProQuest Computer Science Collection Computer and Information Systems Abstracts ProQuest Health & Medical Complete (Alumni) Materials Business File Environmental Sciences and Pollution Management Aerospace Database Copper Technical Reference Library Engineered Materials Abstracts Genetics Abstracts Bacteriology Abstracts (Microbiology B) Algology Mycology and Protozoology Abstracts (Microbiology C) AIDS and Cancer Research Abstracts Chemoreception Abstracts Industrial and Applied Microbiology Abstracts (Microbiology A) Advanced Technologies Database with Aerospace ANTE: Abstracts in New Technology & Engineering Civil Engineering Abstracts Aluminium Industry Abstracts Virology and AIDS Abstracts Electronics & Communications Abstracts Ceramic Abstracts Ecology Abstracts Neurosciences Abstracts METADEX Biotechnology and BioEngineering Abstracts Computer and Information Systems Abstracts Professional Entomology Abstracts Animal Behavior Abstracts Solid State and Superconductivity Abstracts Engineering Research Database Calcium & Calcified Tissue Abstracts Corrosion Abstracts MEDLINE - Academic |
| DatabaseTitleList | MEDLINE - Academic CrossRef Materials Research Database MEDLINE |
| Database_xml | – sequence: 1 dbid: NPM name: PubMed url: https://proxy.k.utb.cz/login?url=http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed sourceTypes: Index Database – sequence: 2 dbid: EIF name: MEDLINE url: https://proxy.k.utb.cz/login?url=https://www.webofscience.com/wos/medline/basic-search sourceTypes: Index Database |
| DeliveryMethod | fulltext_linktorsrc |
| Discipline | Sciences (General) Biology |
| EISSN | 1095-9203 |
| EndPage | 998 |
| ExternalDocumentID | PMC6637967 30819965 10_1126_science_aat7186 26611649 |
| Genre | Journal Article Research Support, N.I.H., Extramural |
| GrantInformation_xml | – fundername: Wellcome Trust – fundername: NIAID NIH HHS grantid: R21 AI117220 – fundername: Howard Hughes Medical Institute – fundername: NIDDK NIH HHS grantid: P30 DK034854 – fundername: NIDDK NIH HHS grantid: R01 DK051362 – fundername: NIDDK NIH HHS grantid: R56 DK053056 – fundername: NICHD NIH HHS grantid: K12 HD000850 – fundername: European Research Council – fundername: NIAID NIH HHS grantid: R01 AI024998 – fundername: NIDDK NIH HHS grantid: R01 DK088199 |
| GroupedDBID | --- --Z -DZ -ET -~X .-4 ..I .55 .DC 08G 0R~ 0WA 123 18M 2FS 2KS 2WC 2XV 34G 36B 39C 3R3 53G 5RE 66. 6OB 6TJ 7X2 7~K 85S 8F7 AABCJ AACGO AAIKC AAMNW AANCE AAWTO ABBHK ABDBF ABDEX ABDQB ABEFU ABIVO ABJNI ABOCM ABPLY ABPPZ ABQIJ ABTLG ABWJO ABZEH ACBEA ACBEC ACGFO ACGFS ACGOD ACIWK ACMJI ACNCT ACPRK ACQOY ACUHS ADDRP ADUKH ADXHL AEGBM AENEX AETEA AEUPB AEXZC AFBNE AFFDN AFFNX AFHKK AFQFN AFRAH AGFXO AGNAY AGSOS AHMBA AIDAL AIDUJ AJGZS ALIPV ALMA_UNASSIGNED_HOLDINGS ALSLI ASPBG AVWKF BKF BLC C45 CS3 DB2 DCCCD DU5 EBS EJD EMOBN F5P FA8 FEDTE HZ~ I.T IAO IEA IGS IH2 IHR INH INR IOF IOV IPO IPSME IPY ISE JAAYA JBMMH JCF JENOY JHFFW JKQEH JLS JLXEF JPM JSG JST KCC L7B LSO LU7 M0P MQT MVM N9A NEJ NHB O9- OCB OFXIZ OGEVE OMK OVD P-O P2P PQQKQ PZZ QS- RHI RXW SA0 SC5 SJN TAE TEORI TN5 TWZ UBW UCV UHB UKR UMD UNMZH UQL USG VVN WH7 WI4 X7M XJF XZL Y6R YK4 YKV YNT YOJ YR2 YR5 YRY YSQ YV5 YWH YYP YZZ ZCA ZE2 ~02 ~G0 ~KM ~ZZ .GJ .GO .HR 0-V 186 3EH 4.4 41~ 42X 4R4 692 79B 7X7 7XC 88E 88I 8AF 8CJ 8FE 8FG 8FH 8FI 8FJ 8G5 8GL 8WZ 97F A6W AADHG AAFWJ AAJYS AAKAS AAYJJ AAYOK AAYXX ABCQX ABDPE ABJCF ABPMR ABUWG ABXSQ ACHIC ACQAM ACTDY ADBBV ADMHC ADQXQ ADULT ADZCM AEUYN AFCHL AFKRA AFQQW AJUXI AQVQM ARALO ARAPS ATCPS AZQEC BBNVY BBWZM BCU BEC BENPR BGLVJ BHPHI BKNYI BKSAR BPHCQ BVXVI C2- C51 CCPQU CITATION CJNVE D0S D1I D1J D1K DWQXO D~A EAU EGS EWM EX3 FYUFA GICCO GNUQQ GUQSH HCIFZ HGD HMCUK HQ3 HTVGU HVGLF IAG IBG IEP IER IPC ISN ITC J5H J9C K-O K6- K9- KB. KQ8 L6V LK5 LK8 LPU M0K M0R M1P M2O M2P M2Q M7P M7R M7S N4W OK1 P62 PATMY PCBAR PDBOC PHGZM PHGZT PQEDU PROAC PSQYO PTHSS PV9 PYCSY QJJ R05 RNS RZL SJFOW SKT UBY UHU UKHRP VOH WOQ WOW X7L XIH XKJ XOL YJ6 YXB YYQ ZCG ZGI ZVL ZVM ZXP ZY4 ~H1 CGR CUY CVF ECM EIF GX1 NPM UIG YCJ ZKG 7QF 7QG 7QL 7QP 7QQ 7QR 7SC 7SE 7SN 7SP 7SR 7SS 7T7 7TA 7TB 7TK 7TM 7U5 7U9 8BQ 8FD C1K F28 FR3 H8D H8G H94 JG9 JQ2 K9. KR7 L7M L~C L~D M7N P64 RC3 7X8 5PM |
| ID | FETCH-LOGICAL-c402t-6631fa0873a4028dd49ca38a18da40ef4890db070f87de092f5bcfb71048ad2e3 |
| ISSN | 0036-8075 1095-9203 |
| IngestDate | Thu Aug 21 14:11:09 EDT 2025 Fri Jul 11 09:19:12 EDT 2025 Fri Jul 25 10:47:00 EDT 2025 Thu Apr 03 07:00:03 EDT 2025 Tue Jul 01 01:51:29 EDT 2025 Thu Apr 24 22:59:07 EDT 2025 Thu Jul 03 21:39:01 EDT 2025 |
| IsDoiOpenAccess | false |
| IsOpenAccess | true |
| IsPeerReviewed | true |
| IsScholarly | true |
| Issue | 6430 |
| Language | English |
| License | Copyright © 2019 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works. |
| LinkModel | OpenURL |
| MergedId | FETCHMERGED-LOGICAL-c402t-6631fa0873a4028dd49ca38a18da40ef4890db070f87de092f5bcfb71048ad2e3 |
| Notes | ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 14 content type line 23 Author contributions: J.G., N.K., S.H., and R.S.B. conceived, designed and interpreted the experiments; J.G., N.K., S.H., J.D.M., T.H., S.Sa., T.G., H.L., J.P.L., S.C.G.-V., S.Su., A.M.L., Y.S., J.D., G.M.F., N.W.P., and M.R.d.Z. carried out the experiments; J.N.G., P.R., R.A.F., K.D.M., A.J.M., and A.K. aided with the interpretation of the data; and J.G., N.K., and R.S.B. wrote the manuscript. All authors were involved in critical revision of the manuscript for important intellectual content. These authors contributed equally to this work. |
| ORCID | 0000-0002-3900-9227 0000-0003-1335-7044 0000-0002-0644-9752 0000-0002-9834-5490 0000-0003-4461-0778 0000-0002-2548-7754 0000-0001-9351-4956 0000-0002-8808-5672 0000-0002-7192-0184 0000-0002-6785-3492 0000-0003-0910-2655 0000-0002-2805-4831 0000-0003-0314-9196 0000-0003-1419-3344 0000-0002-7146-8159 0000-0002-4270-8299 0000-0001-9615-7851 0000-0003-3875-6957 0000-0001-5948-7536 0000-0002-1829-302X 0000-0001-7262-9455 0000-0002-9704-248X |
| PMID | 30819965 |
| PQID | 2187118810 |
| PQPubID | 1256 |
| PageCount | 6 |
| ParticipantIDs | pubmedcentral_primary_oai_pubmedcentral_nih_gov_6637967 proquest_miscellaneous_2187515335 proquest_journals_2187118810 pubmed_primary_30819965 crossref_primary_10_1126_science_aat7186 crossref_citationtrail_10_1126_science_aat7186 jstor_primary_26611649 |
| ProviderPackageCode | CITATION AAYXX |
| PublicationCentury | 2000 |
| PublicationDate | 2019-03-01 |
| PublicationDateYYYYMMDD | 2019-03-01 |
| PublicationDate_xml | – month: 03 year: 2019 text: 2019-03-01 day: 01 |
| PublicationDecade | 2010 |
| PublicationPlace | United States |
| PublicationPlace_xml | – name: United States – name: Washington |
| PublicationTitle | Science (American Association for the Advancement of Science) |
| PublicationTitleAlternate | Science |
| PublicationYear | 2019 |
| Publisher | American Association for the Advancement of Science The American Association for the Advancement of Science |
| Publisher_xml | – name: American Association for the Advancement of Science – name: The American Association for the Advancement of Science |
| References | e_1_3_2_26_2 e_1_3_2_27_2 e_1_3_2_48_2 e_1_3_2_28_2 e_1_3_2_41_2 e_1_3_2_40_2 e_1_3_2_20_2 e_1_3_2_43_2 e_1_3_2_21_2 e_1_3_2_42_2 e_1_3_2_22_2 e_1_3_2_45_2 e_1_3_2_23_2 e_1_3_2_44_2 e_1_3_2_24_2 e_1_3_2_47_2 e_1_3_2_25_2 e_1_3_2_46_2 e_1_3_2_9_2 e_1_3_2_15_2 e_1_3_2_38_2 e_1_3_2_8_2 e_1_3_2_16_2 e_1_3_2_37_2 e_1_3_2_7_2 e_1_3_2_17_2 e_1_3_2_6_2 e_1_3_2_18_2 e_1_3_2_39_2 e_1_3_2_19_2 e_1_3_2_30_2 e_1_3_2_32_2 e_1_3_2_10_2 e_1_3_2_31_2 e_1_3_2_5_2 e_1_3_2_11_2 e_1_3_2_34_2 e_1_3_2_4_2 e_1_3_2_12_2 e_1_3_2_33_2 e_1_3_2_3_2 e_1_3_2_13_2 e_1_3_2_36_2 e_1_3_2_2_2 e_1_3_2_14_2 e_1_3_2_35_2 Harriman G. R. (e_1_3_2_29_2) 1999; 162 |
| References_xml | – ident: e_1_3_2_32_2 doi: 10.3791/1488 – ident: e_1_3_2_19_2 doi: 10.1084/jem.190.7.915 – ident: e_1_3_2_15_2 doi: 10.1007/BF00917328 – ident: e_1_3_2_9_2 doi: 10.1111/imr.12189 – ident: e_1_3_2_33_2 doi: 10.1016/j.cell.2016.04.055 – ident: e_1_3_2_36_2 doi: 10.3791/50556 – ident: e_1_3_2_48_2 doi: 10.1038/mi.2017.22 – ident: e_1_3_2_25_2 doi: 10.1038/nri2322 – ident: e_1_3_2_46_2 doi: 10.1093/nar/27.1.209 – ident: e_1_3_2_5_2 doi: 10.1053/j.gastro.2011.05.033 – ident: e_1_3_2_18_2 doi: 10.1172/JCI85113 – ident: e_1_3_2_45_2 doi: 10.1186/s12865-014-0040-5 – ident: e_1_3_2_13_2 doi: 10.1128/MCB.00779-06 – ident: e_1_3_2_14_2 doi: 10.1053/j.gastro.2013.01.023 – ident: e_1_3_2_10_2 doi: 10.1038/cr.2008.312 – ident: e_1_3_2_6_2 doi: 10.1038/nature12599 – ident: e_1_3_2_8_2 doi: 10.1038/nri3322 – ident: e_1_3_2_24_2 doi: 10.1016/j.immuni.2015.08.007 – ident: e_1_3_2_12_2 doi: 10.1084/jem.20160791 – ident: e_1_3_2_20_2 doi: 10.1126/science.288.5474.2222 – ident: e_1_3_2_37_2 doi: 10.1006/meth.2001.1262 – ident: e_1_3_2_40_2 doi: 10.1186/s13059-014-0550-8 – ident: e_1_3_2_38_2 doi: 10.1038/nbt.4096 – ident: e_1_3_2_22_2 doi: 10.1093/intimm/11.5.643 – ident: e_1_3_2_26_2 doi: 10.1126/science.aan6619 – ident: e_1_3_2_4_2 doi: 10.1016/j.cell.2008.07.021 – ident: e_1_3_2_30_2 doi: 10.1073/pnas.1315792111 – volume: 162 start-page: 2521 year: 1999 ident: e_1_3_2_29_2 article-title: Targeted deletion of the IgA constant region in mice leads to IgA deficiency with alterations in expression of other Ig isotypes publication-title: J. Immunol. doi: 10.4049/jimmunol.162.5.2521 – ident: e_1_3_2_39_2 doi: 10.1093/bioinformatics/bts635 – ident: e_1_3_2_11_2 doi: 10.1053/gast.2001.20912 – ident: e_1_3_2_17_2 doi: 10.1016/j.immuni.2017.06.013 – ident: e_1_3_2_42_2 doi: 10.1093/bioinformatics/btr260 – ident: e_1_3_2_47_2 doi: 10.1371/journal.pcbi.1004503 – ident: e_1_3_2_21_2 doi: 10.1038/mi.2007.6 – ident: e_1_3_2_34_2 doi: 10.1038/nprot.2016.091 – ident: e_1_3_2_23_2 doi: 10.1038/nri2901 – ident: e_1_3_2_7_2 doi: 10.1016/j.cell.2014.08.006 – ident: e_1_3_2_16_2 doi: 10.1126/scitranslmed.aan1217 – ident: e_1_3_2_27_2 doi: 10.1016/S1074-7613(01)00088-7 – ident: e_1_3_2_3_2 doi: 10.1371/journal.pone.0025589 – ident: e_1_3_2_35_2 doi: 10.1126/science.1086907 – ident: e_1_3_2_41_2 doi: 10.1073/pnas.0506580102 – ident: e_1_3_2_2_2 doi: 10.1038/nri.2016.62 – ident: e_1_3_2_28_2 doi: 10.1136/gutjnl-2012-303527 – ident: e_1_3_2_43_2 doi: 10.1016/j.cels.2015.12.004 – ident: e_1_3_2_44_2 doi: 10.1038/nmeth.3364 – ident: e_1_3_2_31_2 doi: 10.1002/gene.20042 |
| SSID | ssj0009593 |
| Score | 2.5041785 |
| Snippet | Immunoglobulin A (IgA) is the major secretory immunoglobulin isotype found at mucosal surfaces, where it regulates microbial commensalism and excludes luminal... Immunoglobulin A (IgA) is the most abundantly expressed antibody isotype and can be found at various mucosal surfaces in the body, including the... Stressed gut epithelium gets some reliefImmunoglobulin A (IgA) is the most abundantly expressed antibody isotype and can be found at various mucosal surfaces... |
| SourceID | pubmedcentral proquest pubmed crossref jstor |
| SourceType | Open Access Repository Aggregation Database Index Database Enrichment Source Publisher |
| StartPage | 993 |
| SubjectTerms | Animals Autophagy Autophagy-Related Proteins - genetics Commensalism Endoplasmic reticulum Endoplasmic Reticulum Stress Epithelial cells Epithelial Cells - immunology Epithelium Gastrointestinal tract Humans Immunity, Mucosal Immunoglobulin A Immunoglobulin A - immunology Immunoglobulins Inflammation Intestinal Mucosa - immunology Lamina propria Lymphocytes Lymphocytes T Mice Mice, Inbred C57BL Mice, Knockout Microbiota Microorganisms Mucosa Peritoneum Phagocytosis Plasma cells Plasma Cells - immunology Stress Tissue Culture Techniques X-Box Binding Protein 1 - genetics |
| Title | Epithelial endoplasmic reticulum stress orchestrates a protective IgA response |
| URI | https://www.jstor.org/stable/26611649 https://www.ncbi.nlm.nih.gov/pubmed/30819965 https://www.proquest.com/docview/2187118810 https://www.proquest.com/docview/2187515335 https://pubmed.ncbi.nlm.nih.gov/PMC6637967 |
| Volume | 363 |
| hasFullText | 1 |
| inHoldings | 1 |
| isFullTextHit | |
| isPrint | |
| link | http://utb.summon.serialssolutions.com/2.0.0/link/0/eLvHCXMwnV3fb9MwELZKJyReEBsMAgMZiYehKZXr_HIeO7ZRJrEXNmlvkZM4dKxLojZ5gL-JP5Jz7LjuaKXBi9UmjpX4LnefnbvvEPpAgpSyImWun4oQGsolByRzvSwKUo-Fkd9t5ny9CKdX_vl1cD0Y_LailtomHWW_NuaV_I9U4RjIVWbJ_oNkzaBwAH6DfKEFCUP7IBmf1jKjYi43vUWZVzUg4buOkrlRu3p9Jki16MpiSVaI5RE_0twMMmboy_cJdO_CZNdigvpXHvCn-aZjSdIEJ05UCEEfUaAvs7YXPgMyb35otH5eidpY-EVb33KljLdzbqD9tFpWd12IwbdZOxM3qy1zGdKgEkngZk5G9n6FTJHqA7Z6G6wpkJUHUmaXyIqRlHi2Xfa05VMKCMiJWIY2VnUVtc-OVSXrv92BVcBSjDhvwBNvIN6-5xBNmGK3QKJhogdI9ACP0A6FRQkdop3J8cnx2VaSZ00lZSVp9fewhoJUIOymJc79SF0L-lw-Q0_1mgVPlALuooEo99BjVcX05x7a1VJf4kNNYv7xObpY6Sa2dBMb3cRKN7Gtm5jjlW5i0E3c6-YLdHV2evlp6uraHW7mE9q4AGTHBScs8jj8Z3nuxxn3GB-zHA6IwmcxyVPwNwWLckFiWgRpVqSAd33Gcyq8fTQsq1K8QpgWNCdBIERKiZ_zCFwGD3wYF5Ap42HooFE_l0mmie1lfZV5skV-Djo0F9SK02V71_1OOKafxLPj0I8ddNBLK9EWYZkAXI5gwc7GxEHvzWmw1_IjHC9F1ao-gVxkBQ56qYRrBvckPo9DOBOtid10kFzw62fKm1nHCQ_zDRMTvX74o71BT1av5wEaNotWvAWA3aTvtF7_AXcV2Gc |
| linkProvider | EBSCOhost |
| openUrl | ctx_ver=Z39.88-2004&ctx_enc=info%3Aofi%2Fenc%3AUTF-8&rfr_id=info%3Asid%2Fsummon.serialssolutions.com&rft_val_fmt=info%3Aofi%2Ffmt%3Akev%3Amtx%3Ajournal&rft.genre=article&rft.atitle=Epithelial+endoplasmic+reticulum+stress+orchestrates+a+protective+IgA+response&rft.jtitle=Science+%28American+Association+for+the+Advancement+of+Science%29&rft.au=Grootjans%2C+Joep&rft.au=Krupka%2C+Niklas&rft.au=Hosomi%2C+Shuhei&rft.au=Matute%2C+Juan+D.&rft.date=2019-03-01&rft.issn=0036-8075&rft.eissn=1095-9203&rft.volume=363&rft.issue=6430&rft.spage=993&rft.epage=998&rft_id=info:doi/10.1126%2Fscience.aat7186&rft.externalDBID=n%2Fa&rft.externalDocID=10_1126_science_aat7186 |
| thumbnail_l | http://covers-cdn.summon.serialssolutions.com/index.aspx?isbn=/lc.gif&issn=0036-8075&client=summon |
| thumbnail_m | http://covers-cdn.summon.serialssolutions.com/index.aspx?isbn=/mc.gif&issn=0036-8075&client=summon |
| thumbnail_s | http://covers-cdn.summon.serialssolutions.com/index.aspx?isbn=/sc.gif&issn=0036-8075&client=summon |