Synovial Fibroblasts Selectively Suppress Th1 Cell Responses through IDO1-Mediated Tryptophan Catabolism
The development of rheumatoid arthritis (RA) is linked to functional changes in synovial fibroblasts (SF) and local infiltration of T lymphocytes. Fibroblasts possess the capacity to suppress T cell responses, although the molecular mechanisms of this suppression remain incompletely understood. In t...
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Published in | The Journal of immunology (1950) Vol. 198; no. 8; pp. 3109 - 3117 |
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Main Authors | , , , , , , , , , , , , , , , |
Format | Journal Article |
Language | English |
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United States
American Association of Immunologists
15.04.2017
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Abstract | The development of rheumatoid arthritis (RA) is linked to functional changes in synovial fibroblasts (SF) and local infiltration of T lymphocytes. Fibroblasts possess the capacity to suppress T cell responses, although the molecular mechanisms of this suppression remain incompletely understood. In this study, we aimed to define the mechanisms by which noninflammatory SF modulate Th cell responses and to determine the immunosuppressive efficacy of RASF. Hence, the influence of SF from osteoarthritis or RA patients on total Th cells or different Th cell subsets of healthy donors was analyzed in vitro. We show that SF strongly suppressed the proliferation of Th cells and the secretion of IFN-γ in a cell contact-independent manner. In cocultures of SF and Th cells, tryptophan was completely depleted within a few days, resulting in eukaryotic initiation factor 2α phosphorylation, TCRζ-chain downregulation, and proliferation arrest. Blocking IDO1 activity completely restored Th cell proliferation, but not IFN-γ production. Interestingly, only the proliferation of Th1 cells, but not of Th2 or Th17 cells, was affected. Finally, RASF had a significantly lower IDO1 expression and a weaker Th cell suppressive capacity compared with osteoarthritis SF. We postulate that the suppression of Th cell growth by SF through tryptophan catabolism may play an important role in preventing inappropriate Th cell responses under normal conditions. However, expansion of Th17 cells that do not induce IDO1-mediated suppression and the reduced capacity of RASF to restrict Th cell proliferation through tryptophan metabolism may support the initiation and propagation of synovitis in RA patients. |
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AbstractList | The development of rheumatoid arthritis (RA) is linked to functional changes in synovial fibroblasts (SF) and local infiltration of T lymphocytes. Fibroblasts possess the capacity to suppress T cell responses, although the molecular mechanisms of this suppression remain incompletely understood. In this study, we aimed to define the mechanisms by which noninflammatory SF modulate Th cell responses and to determine the immunosuppressive efficacy of RASF. Hence, the influence of SF from osteoarthritis or RA patients on total Th cells or different Th cell subsets of healthy donors was analyzed in vitro. We show that SF strongly suppressed the proliferation of Th cells and the secretion of IFN-γ in a cell contact-independent manner. In cocultures of SF and Th cells, tryptophan was completely depleted within a few days, resulting in eukaryotic initiation factor 2α phosphorylation, TCRζ-chain downregulation, and proliferation arrest. Blocking IDO1 activity completely restored Th cell proliferation, but not IFN-γ production. Interestingly, only the proliferation of Th1 cells, but not of Th2 or Th17 cells, was affected. Finally, RASF had a significantly lower IDO1 expression and a weaker Th cell suppressive capacity compared with osteoarthritis SF. We postulate that the suppression of Th cell growth by SF through tryptophan catabolism may play an important role in preventing inappropriate Th cell responses under normal conditions. However, expansion of Th17 cells that do not induce IDO1-mediated suppression and the reduced capacity of RASF to restrict Th cell proliferation through tryptophan metabolism may support the initiation and propagation of synovitis in RA patients. The development of rheumatoid arthritis (RA) is linked to functional changes in synovial fibroblasts (SF) and local infiltration of T lymphocytes. Fibroblasts possess the capacity to suppress T cell responses, although the molecular mechanisms of this suppression remain incompletely understood. In this study, we aimed to define the mechanisms by which noninflammatory SF modulate Th cell responses and to determine the immunosuppressive efficacy of RASF. Hence, the influence of SF from osteoarthritis or RA patients on total Th cells or different Th cell subsets of healthy donors was analyzed in vitro. We show that SF strongly suppressed the proliferation of Th cells and the secretion of IFN- gamma in a cell contact-independent manner. In cocultures of SF and Th cells, tryptophan was completely depleted within a few days, resulting in eukaryotic initiation factor 2 alpha phosphorylation, TCR zeta -chain downregulation, and proliferation arrest. Blocking IDO1 activity completely restored Th cell proliferation, but not IFN- gamma production. Interestingly, only the proliferation of Th1 cells, but not of Th2 or Th17 cells, was affected. Finally, RASF had a significantly lower IDO1 expression and a weaker Th cell suppressive capacity compared with osteoarthritis SF. We postulate that the suppression of Th cell growth by SF through tryptophan catabolism may play an important role in preventing inappropriate Th cell responses under normal conditions. However, expansion of Th17 cells that do not induce IDO1-mediated suppression and the reduced capacity of RASF to restrict Th cell proliferation through tryptophan metabolism may support the initiation and propagation of synovitis in RA patients. |
Author | Neidhart, Michel Mohapatra, Soumya R Platten, Michael Saikali, Philippe Krienke, Stefan Lorenz, Hanns-Martin Bohnen, Antonia Tykocinski, Lars-Oliver Kaul, Nathalie-Christin Opitz, Christiane A Löhning, Max Gay, Steffen Tretter, Theresa Oezen, Iris Lauffer, Anna M Adam, Isabell |
Author_xml | – sequence: 1 givenname: Lars-Oliver surname: Tykocinski fullname: Tykocinski, Lars-Oliver email: lars.tykocinski@med.uni-heidelberg.de organization: Division of Rheumatology, Department of Medicine V, University of Heidelberg, 69120 Heidelberg, Germany; lars.tykocinski@med.uni-heidelberg.de – sequence: 2 givenname: Anna M surname: Lauffer fullname: Lauffer, Anna M organization: Division of Rheumatology, Department of Medicine V, University of Heidelberg, 69120 Heidelberg, Germany – sequence: 3 givenname: Antonia surname: Bohnen fullname: Bohnen, Antonia organization: Division of Rheumatology, Department of Medicine V, University of Heidelberg, 69120 Heidelberg, Germany – sequence: 4 givenname: Nathalie-Christin surname: Kaul fullname: Kaul, Nathalie-Christin organization: Division of Rheumatology, Department of Medicine V, University of Heidelberg, 69120 Heidelberg, Germany – sequence: 5 givenname: Stefan surname: Krienke fullname: Krienke, Stefan organization: Division of Rheumatology, Department of Medicine V, University of Heidelberg, 69120 Heidelberg, Germany – sequence: 6 givenname: Theresa surname: Tretter fullname: Tretter, Theresa organization: Division of Rheumatology, Department of Medicine V, University of Heidelberg, 69120 Heidelberg, Germany – sequence: 7 givenname: Isabell surname: Adam fullname: Adam, Isabell organization: Brain Cancer Metabolism, German Cancer Research Center, 69120 Heidelberg, Germany – sequence: 8 givenname: Soumya R orcidid: 0000-0002-4350-6410 surname: Mohapatra fullname: Mohapatra, Soumya R organization: Brain Cancer Metabolism, German Cancer Research Center, 69120 Heidelberg, Germany – sequence: 9 givenname: Philippe surname: Saikali fullname: Saikali, Philippe organization: Experimental Immunology, German Rheumatism Research Center, 10117 Berlin, Germany – sequence: 10 givenname: Max surname: Löhning fullname: Löhning, Max organization: Experimental Immunology, German Rheumatism Research Center, 10117 Berlin, Germany – sequence: 11 givenname: Michel surname: Neidhart fullname: Neidhart, Michel organization: Department of Rheumatology, University Hospital Zurich, 8091 Zurich, Switzerland; and – sequence: 12 givenname: Steffen orcidid: 0000-0002-2920-9268 surname: Gay fullname: Gay, Steffen organization: Department of Rheumatology, University Hospital Zurich, 8091 Zurich, Switzerland; and – sequence: 13 givenname: Iris surname: Oezen fullname: Oezen, Iris organization: Neuroimmunology, German Cancer Research Center, 69120 Heidelberg, Germany – sequence: 14 givenname: Michael surname: Platten fullname: Platten, Michael organization: Neuroimmunology, German Cancer Research Center, 69120 Heidelberg, Germany – sequence: 15 givenname: Christiane A orcidid: 0000-0001-5575-9821 surname: Opitz fullname: Opitz, Christiane A organization: Brain Cancer Metabolism, German Cancer Research Center, 69120 Heidelberg, Germany – sequence: 16 givenname: Hanns-Martin surname: Lorenz fullname: Lorenz, Hanns-Martin organization: Division of Rheumatology, Department of Medicine V, University of Heidelberg, 69120 Heidelberg, Germany |
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Cites_doi | 10.1089/hum.2009.217 10.1002/art.27584 10.1080/2162402X.2016.1274477 10.1182/blood-2005-08-3507 10.1038/nature10491 10.1016/S1097-2765(03)00105-9 10.3899/jrheum.141505 10.1007/s00018-007-7140-9 10.3727/096368910X536545 10.1182/blood-2005-03-0979 10.1002/art.25018 10.1016/j.immuni.2005.03.013 10.1186/ar2205 10.1002/stem.7 10.1007/s10067-011-1737-y 10.4049/jimmunol.176.11.6752 10.4049/jimmunol.179.3.1595 10.4049/jimmunol.163.1.491 10.1186/ar2107 10.1038/82763 10.1016/j.it.2012.10.001 10.2337/db09-1560 10.1007/s10875-010-9415-4 10.1016/j.immuni.2014.01.014 10.1002/eji.201344184 10.1097/BOR.0000000000000036 10.1038/nrrheum.2012.190 10.1016/j.it.2011.11.004 10.1002/art.38574 10.4049/jimmunol.177.11.8226 10.1111/j.0105-2896.2009.00859.x 10.4049/jimmunol.180.11.7423 10.1136/annrheumdis-2014-206965 10.1002/art.21930 10.1038/sj.jid.5700022 10.1002/art.24446 10.1186/ar2477 10.1053/j.gastro.2008.07.016 10.1002/art.27622 10.1186/ar1478 10.4049/jimmunol.0900986 10.1093/rheumatology/ket414 10.1007/s11010-007-9635-y 10.4049/jimmunol.171.11.6173 10.1016/j.autrev.2012.02.019 10.1016/S1471-4906(01)01863-4 10.4049/jimmunol.1300274 10.4049/jimmunol.179.5.2824 10.1002/art.21832 10.4049/jimmunol.1400486 |
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References | Pinchuk (2023010209052539100_r27) 2008; 135 Criado (2023010209052539100_r50) 2009; 60 Forouzandeh (2023010209052539100_r37) 2008; 309 Cappellesso-Fleury (2023010209052539100_r22) 2010; 30 Fallarino (2023010209052539100_r34) 2006; 176 Dewi (2023010209052539100_r25) 2017 Shi (2023010209052539100_r26) 2012; 33 Chen (2023010209052539100_r48) 2011; 22 Munn (2023010209052539100_r30) 2013; 34 Skapenko (2023010209052539100_r44) 1999; 163 Aletaha (2023010209052539100_r24) 2010; 62 Haniffa (2023010209052539100_r20) 2007; 179 Gizinski (2023010209052539100_r14) 2014; 26 Lundy (2023010209052539100_r15) 2007; 9 Cope (2023010209052539100_r43) 2007; 25 Munn (2023010209052539100_r35) 2005; 22 Opitz (2023010209052539100_r23) 2009; 27 Prots (2023010209052539100_r45) 2006; 54 Szántó (2023010209052539100_r49) 2007; 9 Braun (2023010209052539100_r28) 2005; 106 Pène (2023010209052539100_r40) 2008; 180 Jalili (2023010209052539100_r47) 2010; 59 Leipe (2023010209052539100_r38) 2010; 62 Metawi (2023010209052539100_r18) 2011; 30 Nakae (2023010209052539100_r19) 2003; 171 Neidhart (2023010209052539100_r10) 2014; 66 Kang (2023010209052539100_r52) 2015; 42 Shimabukuro (2023010209052539100_r7) 1992; 76 Pradier (2023010209052539100_r4) 2011; 20 Benedetti (2023010209052539100_r13) 2014; 44 Donlin (2023010209052539100_r3) 2014; 193 Harding (2023010209052539100_r33) 2003; 11 Zhu (2023010209052539100_r51) 2006; 177 Störch (2023010209052539100_r8) 2016; 75 Shahrara (2023010209052539100_r39) 2008; 10 Kurashima (2023010209052539100_r5) 2014; 40 Paulissen (2023010209052539100_r42) 2013; 191 Jones (2023010209052539100_r21) 2007; 179 Furst (2023010209052539100_r16) 2014; 53 Opitz (2023010209052539100_r32) 2007; 64 Baban (2023010209052539100_r36) 2009; 183 Filer (2023010209052539100_r6) 2006; 54 Dong (2023010209052539100_r41) 2012; 11 Li (2023010209052539100_r46) 2006; 126 Bottini (2023010209052539100_r11) 2013; 9 Lubberts (2023010209052539100_r17) 2005; 7 Bartok (2023010209052539100_r1) 2010; 233 Chomarat (2023010209052539100_r2) 2000; 1 Karouzakis (2023010209052539100_r12) 2009; 60 Buckley (2023010209052539100_r9) 2001; 22 Opitz (2023010209052539100_r31) 2011; 478 von Bergwelt-Baildon (2023010209052539100_r29) 2006; 108 |
References_xml | – volume: 22 start-page: 145 year: 2011 ident: 2023010209052539100_r48 article-title: Amelioration of rat collagen-induced arthritis through CD4+ T cells apoptosis and synovial interleukin-17 reduction by indoleamine 2,3-dioxygenase gene therapy. publication-title: Hum. Gene Ther. doi: 10.1089/hum.2009.217 contributor: fullname: Chen – volume: 62 start-page: 2569 year: 2010 ident: 2023010209052539100_r24 article-title: 2010 Rheumatoid arthritis classification criteria: an American College of Rheumatology/European League against Rheumatism collaborative initiative. publication-title: Arthritis Rheum. doi: 10.1002/art.27584 contributor: fullname: Aletaha – year: 2017 ident: 2023010209052539100_r25 article-title: Suppression of indoleamine-2,3-dioxygenase 1 expression by promoter hypermethylation in ER-positive breast cancer. publication-title: OncoImmunology. doi: 10.1080/2162402X.2016.1274477 contributor: fullname: Dewi – volume: 108 start-page: 228 year: 2006 ident: 2023010209052539100_r29 article-title: CD25 and indoleamine 2,3-dioxygenase are up-regulated by prostaglandin E2 and expressed by tumor-associated dendritic cells in vivo: additional mechanisms of T-cell inhibition. publication-title: Blood doi: 10.1182/blood-2005-08-3507 contributor: fullname: von Bergwelt-Baildon – volume: 478 start-page: 197 year: 2011 ident: 2023010209052539100_r31 article-title: An endogenous tumour-promoting ligand of the human aryl hydrocarbon receptor. publication-title: Nature doi: 10.1038/nature10491 contributor: fullname: Opitz – volume: 11 start-page: 619 year: 2003 ident: 2023010209052539100_r33 article-title: An integrated stress response regulates amino acid metabolism and resistance to oxidative stress. publication-title: Mol. Cell doi: 10.1016/S1097-2765(03)00105-9 contributor: fullname: Harding – volume: 42 start-page: 2003 year: 2015 ident: 2023010209052539100_r52 article-title: Downregulation of tryptophan-related metabolomic profile in rheumatoid arthritis synovial fluid. publication-title: J. Rheumatol. doi: 10.3899/jrheum.141505 contributor: fullname: Kang – volume: 64 start-page: 2542 year: 2007 ident: 2023010209052539100_r32 article-title: Tryptophan degradation in autoimmune diseases. publication-title: Cell. Mol. Life Sci. doi: 10.1007/s00018-007-7140-9 contributor: fullname: Opitz – volume: 20 start-page: 681 year: 2011 ident: 2023010209052539100_r4 article-title: Human bone marrow stromal cells and skin fibroblasts inhibit natural killer cell proliferation and cytotoxic activity. publication-title: Cell Transplant. doi: 10.3727/096368910X536545 contributor: fullname: Pradier – volume: 106 start-page: 2375 year: 2005 ident: 2023010209052539100_r28 article-title: A two-step induction of indoleamine 2,3 dioxygenase (IDO) activity during dendritic-cell maturation. publication-title: Blood doi: 10.1182/blood-2005-03-0979 contributor: fullname: Braun – volume: 60 start-page: 3613 year: 2009 ident: 2023010209052539100_r12 article-title: DNA hypomethylation in rheumatoid arthritis synovial fibroblasts. publication-title: Arthritis Rheum. doi: 10.1002/art.25018 contributor: fullname: Karouzakis – volume: 22 start-page: 633 year: 2005 ident: 2023010209052539100_r35 article-title: GCN2 kinase in T cells mediates proliferative arrest and anergy induction in response to indoleamine 2,3-dioxygenase. publication-title: Immunity doi: 10.1016/j.immuni.2005.03.013 contributor: fullname: Munn – volume: 9 start-page: R50 year: 2007 ident: 2023010209052539100_r49 article-title: Inhibition of indoleamine 2,3-dioxygenase-mediated tryptophan catabolism accelerates collagen-induced arthritis in mice. publication-title: Arthritis Res. Ther. doi: 10.1186/ar2205 contributor: fullname: Szántó – volume: 27 start-page: 909 year: 2009 ident: 2023010209052539100_r23 article-title: Toll-like receptor engagement enhances the immunosuppressive properties of human bone marrow-derived mesenchymal stem cells by inducing indoleamine-2,3-dioxygenase-1 via interferon-beta and protein kinase R. publication-title: Stem Cells doi: 10.1002/stem.7 contributor: fullname: Opitz – volume: 30 start-page: 1201 year: 2011 ident: 2023010209052539100_r18 article-title: Serum and synovial fluid levels of interleukin-17 in correlation with disease activity in patients with RA. publication-title: Clin. Rheumatol. doi: 10.1007/s10067-011-1737-y contributor: fullname: Metawi – volume: 176 start-page: 6752 year: 2006 ident: 2023010209052539100_r34 article-title: The combined effects of tryptophan starvation and tryptophan catabolites down-regulate T cell receptor ζ-chain and induce a regulatory phenotype in naive T cells. publication-title: J. Immunol. doi: 10.4049/jimmunol.176.11.6752 contributor: fullname: Fallarino – volume: 179 start-page: 1595 year: 2007 ident: 2023010209052539100_r20 article-title: Adult human fibroblasts are potent immunoregulatory cells and functionally equivalent to mesenchymal stem cells. publication-title: J. Immunol. doi: 10.4049/jimmunol.179.3.1595 contributor: fullname: Haniffa – volume: 163 start-page: 491 year: 1999 ident: 2023010209052539100_r44 article-title: Altered memory T cell differentiation in patients with early rheumatoid arthritis. publication-title: J. Immunol. doi: 10.4049/jimmunol.163.1.491 contributor: fullname: Skapenko – volume: 9 start-page: 202 year: 2007 ident: 2023010209052539100_r15 article-title: Cells of the synovium in rheumatoid arthritis. T lymphocytes. publication-title: Arthritis Res. Ther. doi: 10.1186/ar2107 contributor: fullname: Lundy – volume: 1 start-page: 510 year: 2000 ident: 2023010209052539100_r2 article-title: IL-6 switches the differentiation of monocytes from dendritic cells to macrophages. publication-title: Nat. Immunol. doi: 10.1038/82763 contributor: fullname: Chomarat – volume: 34 start-page: 137 year: 2013 ident: 2023010209052539100_r30 article-title: Indoleamine 2,3 dioxygenase and metabolic control of immune responses. publication-title: Trends Immunol. doi: 10.1016/j.it.2012.10.001 contributor: fullname: Munn – volume: 59 start-page: 2219 year: 2010 ident: 2023010209052539100_r47 article-title: Local expression of indoleamine 2,3 dioxygenase in syngeneic fibroblasts significantly prolongs survival of an engineered three-dimensional islet allograft. publication-title: Diabetes doi: 10.2337/db09-1560 contributor: fullname: Jalili – volume: 30 start-page: 607 year: 2010 ident: 2023010209052539100_r22 article-title: Human fibroblasts share immunosuppressive properties with bone marrow mesenchymal stem cells. publication-title: J. Clin. Immunol. doi: 10.1007/s10875-010-9415-4 contributor: fullname: Cappellesso-Fleury – volume: 40 start-page: 530 year: 2014 ident: 2023010209052539100_r5 article-title: The enzyme Cyp26b1 mediates inhibition of mast cell activation by fibroblasts to maintain skin-barrier homeostasis. publication-title: Immunity doi: 10.1016/j.immuni.2014.01.014 contributor: fullname: Kurashima – volume: 44 start-page: 339 year: 2014 ident: 2023010209052539100_r13 article-title: Interleukin 17 contributes to the chronicity of inflammatory diseases such as rheumatoid arthritis. publication-title: Eur. J. Immunol. doi: 10.1002/eji.201344184 contributor: fullname: Benedetti – volume: 26 start-page: 204 year: 2014 ident: 2023010209052539100_r14 article-title: T cell subsets and their role in the pathogenesis of rheumatic disease. publication-title: Curr. Opin. Rheumatol. doi: 10.1097/BOR.0000000000000036 contributor: fullname: Gizinski – volume: 9 start-page: 24 year: 2013 ident: 2023010209052539100_r11 article-title: Duality of fibroblast-like synoviocytes in RA: passive responders and imprinted aggressors. publication-title: Nat. Rev. Rheumatol. doi: 10.1038/nrrheum.2012.190 contributor: fullname: Bottini – volume: 33 start-page: 136 year: 2012 ident: 2023010209052539100_r26 article-title: How mesenchymal stem cells interact with tissue immune responses. publication-title: Trends Immunol. doi: 10.1016/j.it.2011.11.004 contributor: fullname: Shi – volume: 66 start-page: 1723 year: 2014 ident: 2023010209052539100_r10 article-title: Inhibition of spermidine/spermine N1-acetyltransferase activity: a new therapeutic concept in rheumatoid arthritis. publication-title: Arthritis Rheumatol. doi: 10.1002/art.38574 contributor: fullname: Neidhart – volume: 76 start-page: 344 year: 1992 ident: 2023010209052539100_r7 article-title: Interferon-gamma-dependent immunosuppressive effects of human gingival fibroblasts. publication-title: Immunology contributor: fullname: Shimabukuro – volume: 177 start-page: 8226 year: 2006 ident: 2023010209052539100_r51 article-title: Synovial autoreactive T cells in rheumatoid arthritis resist IDO-mediated inhibition. publication-title: J. Immunol. doi: 10.4049/jimmunol.177.11.8226 contributor: fullname: Zhu – volume: 233 start-page: 233 year: 2010 ident: 2023010209052539100_r1 article-title: Fibroblast-like synoviocytes: key effector cells in rheumatoid arthritis. publication-title: Immunol. Rev. doi: 10.1111/j.0105-2896.2009.00859.x contributor: fullname: Bartok – volume: 180 start-page: 7423 year: 2008 ident: 2023010209052539100_r40 article-title: Chronically inflamed human tissues are infiltrated by highly differentiated Th17 lymphocytes. publication-title: J. Immunol. doi: 10.4049/jimmunol.180.11.7423 contributor: fullname: Pène – volume: 75 start-page: 924 year: 2016 ident: 2023010209052539100_r8 article-title: Activated human B cells induce inflammatory fibroblasts with cartilage-destructive properties and become functionally suppressed in return. publication-title: Ann. Rheum. Dis. doi: 10.1136/annrheumdis-2014-206965 contributor: fullname: Störch – volume: 54 start-page: 2096 year: 2006 ident: 2023010209052539100_r6 article-title: Differential survival of leukocyte subsets mediated by synovial, bone marrow, and skin fibroblasts: site-specific versus activation-dependent survival of T cells and neutrophils. publication-title: Arthritis Rheum. doi: 10.1002/art.21930 contributor: fullname: Filer – volume: 126 start-page: 128 year: 2006 ident: 2023010209052539100_r46 article-title: Local expression of indoleamine 2,3-dioxygenase protects engraftment of xenogeneic skin substitute. publication-title: J. Invest. Dermatol. doi: 10.1038/sj.jid.5700022 contributor: fullname: Li – volume: 60 start-page: 1342 year: 2009 ident: 2023010209052539100_r50 article-title: Indoleamine 2,3 dioxygenase-mediated tryptophan catabolism regulates accumulation of Th1/Th17 cells in the joint in collagen-induced arthritis. publication-title: Arthritis Rheum. doi: 10.1002/art.24446 contributor: fullname: Criado – volume: 10 start-page: R93 year: 2008 ident: 2023010209052539100_r39 article-title: TH-17 cells in rheumatoid arthritis. publication-title: Arthritis Res. Ther. doi: 10.1186/ar2477 contributor: fullname: Shahrara – volume: 135 start-page: 1228 year: 2008 ident: 2023010209052539100_r27 article-title: PD-1 ligand expression by human colonic myofibroblasts/fibroblasts regulates CD4+ T-cell activity. publication-title: Gastroenterology doi: 10.1053/j.gastro.2008.07.016 contributor: fullname: Pinchuk – volume: 62 start-page: 2876 year: 2010 ident: 2023010209052539100_r38 article-title: Role of Th17 cells in human autoimmune arthritis. publication-title: Arthritis Rheum. doi: 10.1002/art.27622 contributor: fullname: Leipe – volume: 7 start-page: 29 year: 2005 ident: 2023010209052539100_r17 article-title: The role of T-cell interleukin-17 in conducting destructive arthritis: lessons from animal models. publication-title: Arthritis Res. Ther. doi: 10.1186/ar1478 contributor: fullname: Lubberts – volume: 183 start-page: 2475 year: 2009 ident: 2023010209052539100_r36 article-title: IDO activates regulatory T cells and blocks their conversion into Th17-like T cells. publication-title: J. Immunol. doi: 10.4049/jimmunol.0900986 contributor: fullname: Baban – volume: 53 start-page: 1560 year: 2014 ident: 2023010209052539100_r16 article-title: Rheumatoid arthritis pathophysiology: update on emerging cytokine and cytokine-associated cell targets. publication-title: Rheumatology (Oxford) doi: 10.1093/rheumatology/ket414 contributor: fullname: Furst – volume: 309 start-page: 1 year: 2008 ident: 2023010209052539100_r37 article-title: Differential immunosuppressive effect of indoleamine 2,3-dioxygenase (IDO) on primary human CD4+ and CD8+ T cells. publication-title: Mol. Cell. Biochem. doi: 10.1007/s11010-007-9635-y contributor: fullname: Forouzandeh – volume: 171 start-page: 6173 year: 2003 ident: 2023010209052539100_r19 article-title: Suppression of immune induction of collagen-induced arthritis in IL-17-deficient mice. publication-title: J. Immunol. doi: 10.4049/jimmunol.171.11.6173 contributor: fullname: Nakae – volume: 11 start-page: 844 year: 2012 ident: 2023010209052539100_r41 article-title: Functional niche of inflamed synovium for Th17-cell expansion and activation in rheumatoid arthritis: implication to clinical therapeutics. publication-title: Autoimmun. Rev. doi: 10.1016/j.autrev.2012.02.019 contributor: fullname: Dong – volume: 22 start-page: 199 year: 2001 ident: 2023010209052539100_r9 article-title: Fibroblasts regulate the switch from acute resolving to chronic persistent inflammation. publication-title: Trends Immunol. doi: 10.1016/S1471-4906(01)01863-4 contributor: fullname: Buckley – volume: 191 start-page: 1364 year: 2013 ident: 2023010209052539100_r42 article-title: Synovial fibroblasts directly induce Th17 pathogenicity via the cyclooxygenase/prostaglandin E2 pathway, independent of IL-23. publication-title: J. Immunol. doi: 10.4049/jimmunol.1300274 contributor: fullname: Paulissen – volume: 179 start-page: 2824 year: 2007 ident: 2023010209052539100_r21 article-title: The antiproliferative effect of mesenchymal stem cells is a fundamental property shared by all stromal cells. publication-title: J. Immunol. doi: 10.4049/jimmunol.179.5.2824 contributor: fullname: Jones – volume: 54 start-page: 1491 year: 2006 ident: 2023010209052539100_r45 article-title: Association of the IL4R single-nucleotide polymorphism I50V with rapidly erosive rheumatoid arthritis. publication-title: Arthritis Rheum. doi: 10.1002/art.21832 contributor: fullname: Prots – volume: 193 start-page: 2373 year: 2014 ident: 2023010209052539100_r3 article-title: Modulation of TNF-induced macrophage polarization by synovial fibroblasts. publication-title: J. Immunol. doi: 10.4049/jimmunol.1400486 contributor: fullname: Donlin – volume: 25 start-page: S4 year: 2007 ident: 2023010209052539100_r43 article-title: The central role of T cells in rheumatoid arthritis. publication-title: Clin. Exp. Rheumatol. contributor: fullname: Cope |
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SubjectTerms | Arthritis Arthritis, Rheumatoid - immunology Catabolism Cell Differentiation - immunology Cell growth Cell proliferation Chromatography, High Pressure Liquid Coculture Techniques Fibroblasts Fibroblasts - immunology Fibroblasts - metabolism Helper cells Humans Immunoblotting Immunosuppression Indoleamine-Pyrrole 2,3,-Dioxygenase - immunology Indoleamine-Pyrrole 2,3,-Dioxygenase - metabolism Interferon Lymphocyte Activation - immunology Lymphocytes Lymphocytes T Metabolism Molecular modelling Osteoarthritis Osteoarthritis - immunology Phosphorylation Polymerase Chain Reaction Rheumatoid arthritis Synovial Membrane - immunology Synovitis T cell receptors Th1 Cells - immunology Th17 Cells - immunology Th2 Cells - immunology Tryptophan Tryptophan - immunology Tryptophan - metabolism γ-Interferon |
Title | Synovial Fibroblasts Selectively Suppress Th1 Cell Responses through IDO1-Mediated Tryptophan Catabolism |
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