A Positive Feedback Loop of IL-21 Signaling Provoked by Homeostatic CD4(+)CD25(-) T Cell Expansion Is Essential for the Development of Arthritis in Autoimmune K/BxN Mice
DC Field | Value | Language |
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dc.contributor.author | Jang, Eunkyeong | - |
dc.contributor.author | Cho, Sin-Hye | - |
dc.contributor.author | Park, Hyunjoo | - |
dc.contributor.author | Paik, Doo-Jin | - |
dc.contributor.author | Kim, Jung Mogg | - |
dc.contributor.author | Youn, Jeehee | - |
dc.date.accessioned | 2022-12-20T22:50:14Z | - |
dc.date.available | 2022-12-20T22:50:14Z | - |
dc.date.created | 2022-08-26 | - |
dc.date.issued | 2009-04 | - |
dc.identifier.issn | 0022-1767 | - |
dc.identifier.uri | https://scholarworks.bwise.kr/hanyang/handle/2021.sw.hanyang/177033 | - |
dc.description.abstract | Rheumatoid arthritis is a joint-specific autoimmune inflammatory disease of unknown etiology. The K/BxN mouse is a model of rheumatoid arthritis that is thought to be mainly due to autoantibody-mediated inflammatory responses. We showed previously that homeostatic proliferation of autoreactive CD4(+) T cells is required for disease initiation in-the K/BxN mice. In this study, we show that the homeostatically proliferating CD4(+)CD25(-) T cells produce IL-21. We generated IL-21R-deficient (IL-21R(-/-)) K/BxN mice and found that these mice were completely refractory to the development of spontaneous arthritis. They contained fewer CD4(+) T cells with a reduced proportion of homeostatically proliferating cells, fewer follicular Th cells, and, surprisingly, more Th17 cells than their control counterparts. They also failed to develop IgG1(+) memory B cells and autoantigen-specific IgG1 Ab-secreting cells. IL-21 induced expression of receptor activator of NF-kappa B ligand (RANKL) a regulator of osteoclastogenesis, and few RANKL-expressing infiltrates were found in the synovia of IL-21R(-/-) K/BxN mice. Thus, our results demonstrate that IL-21 forms a positive feedback autocrine loop involving homeostatically activated CD4(+) cells and that it plays an essential role in the development of autoimmune arthritis by mechanisms dependent on follicular Th cell development, autoreactive B cell maturation, and RANKL induction but independent of Th17 cell function. Consistent with this, in vivo administration of soluble the IL-21R-Fc fusion protein delayed the onset and progression of arthritis. Our findings suggest that effective targeting of IL-21-mediated processes may be useful in treating autoimmune arthritis. | - |
dc.language | 영어 | - |
dc.language.iso | en | - |
dc.publisher | AMER ASSOC IMMUNOLOGISTS | - |
dc.title | A Positive Feedback Loop of IL-21 Signaling Provoked by Homeostatic CD4(+)CD25(-) T Cell Expansion Is Essential for the Development of Arthritis in Autoimmune K/BxN Mice | - |
dc.type | Article | - |
dc.contributor.affiliatedAuthor | Paik, Doo-Jin | - |
dc.contributor.affiliatedAuthor | Kim, Jung Mogg | - |
dc.contributor.affiliatedAuthor | Youn, Jeehee | - |
dc.identifier.doi | 10.4049/jimmunol.0804350 | - |
dc.identifier.scopusid | 2-s2.0-65249180981 | - |
dc.identifier.wosid | 000265004700023 | - |
dc.identifier.bibliographicCitation | JOURNAL OF IMMUNOLOGY, v.182, no.8, pp.4649 - 4656 | - |
dc.relation.isPartOf | JOURNAL OF IMMUNOLOGY | - |
dc.citation.title | JOURNAL OF IMMUNOLOGY | - |
dc.citation.volume | 182 | - |
dc.citation.number | 8 | - |
dc.citation.startPage | 4649 | - |
dc.citation.endPage | 4656 | - |
dc.type.rims | ART | - |
dc.type.docType | Article | - |
dc.description.journalClass | 1 | - |
dc.description.isOpenAccess | N | - |
dc.description.journalRegisteredClass | scie | - |
dc.description.journalRegisteredClass | scopus | - |
dc.relation.journalResearchArea | Immunology | - |
dc.relation.journalWebOfScienceCategory | Immunology | - |
dc.subject.keywordPlus | FOLLICULAR-HELPER-CELLS | - |
dc.subject.keywordPlus | SELF-REACTIVITY | - |
dc.subject.keywordPlus | RECEPTOR | - |
dc.subject.keywordPlus | GENERATION | - |
dc.subject.keywordPlus | DISEASE | - |
dc.subject.keywordPlus | INTERLEUKIN-21 | - |
dc.subject.keywordPlus | OSTEOCLASTOGENESIS | - |
dc.subject.keywordPlus | DIFFERENTIATION | - |
dc.subject.keywordPlus | PROLIFERATION | - |
dc.subject.keywordPlus | ACTIVATION | - |
dc.identifier.url | https://www.jimmunol.org/content/182/8/4649 | - |
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