Location of CD4+ T cell priming regulates the differentiation of Th1 and Th17 cells and their contribution to arthritis.
Location of CD4+ T cell priming regulates the differentiation of Th1 and Th17 cells and their contribution to arthritis.
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DOI：
10.4049/jimmunol.1203045
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发表时间：
2013-06-01
期刊：
影响因子：
--
通讯作者：
Finnegan A
中科院分区：
文献类型：
--
作者：
Rodeghero R;Cao Y;Olalekan SA;Iwakua Y;Glant TT;Finnegan A
T辅助细胞（Th）细胞因子IFN-γ和IL-17与自身免疫性疾病的发展有关。在类风湿性关节炎（RA）即蛋白聚糖（PG）诱导的关节炎（PGIA）的模型中，需要IFN-γ，而在胶原诱导的关节炎中，IL-17对于关节炎的发展是必需的。在这里，我们表明免疫途径决定了关节炎对IFN-γ或IL-17的需求。腹膜内（i. p.）用PG免疫诱导了CD 4 + T细胞IFN-γ应答，在脾和外周淋巴结中几乎没有IL-17。然而，s.c.免疫在脾和LN中诱导IFN-γ和IL-17 CD 4 + T细胞应答。腹膜内免疫后未能诱导CD 4 + T细胞IL-17应答与T细胞引发有关，因为体外活化的幼稚T细胞完全能够产生IL-17。此外，通过将免疫途径从i. p.改变为s.c.，PGIA从IFN-γ转化为IL-17介导的疾病。关节炎症（细胞炎症和骨侵蚀）的组织学外观在i. p.与s.c.中相似。尽管仅在s.c.次免疫这些数据表明，关节炎易感性所需的初始T细胞引发和Th细胞因子的网站的关键作用。我们的研究结果表明，RA患者不同解剖部位的T细胞活化可能会使T细胞倾向于产生IFN-γ或IL-17。
T helper (Th) cytokines IFN-γ and IL-17 are linked to the development of autoimmune disease. In models of rheumatoid arthritis (RA) i.e. proteoglycan (PG) -induced arthritis (PGIA), IFN-γ is required whereas in collagen-induced arthritis, IL-17 is necessary for development of arthritis. Here we show that the route of immunization determines the requirement for either IFN-γ or IL-17 in arthritis. Intraperitoneal (i.p.) immunization with PG induces a CD4+ T cell IFN-γ response with little IL-17 in the spleen and peripheral lymph nodes. However, s.c. immunization induces both an IFN-γ and an IL-17 CD4+ T cell response in spleen and LNs. The failure to induce a CD4+ T cell IL-17 response after i.p. immunization is associated with T cell priming as naïve T cells activated in vitro were fully capable of producing IL-17. Moreover, PGIA is converted from an IFN-γ to an IL-17-mediated disease by altering the route of immunization from i.p. to s.c. The histological appearance of joint inflammation (cellular inflammation and bone erosion) are similar in the i.p. versus s.c. immunized mice despite the presence of CD4+ T cells producing IL-17 in joint tissues only after s.c. immunization. These data indicate a critical role for the site of initial T cell priming and the Th cytokines required for susceptibility to arthritis. Our findings suggest that T cell activation at different anatomical sites in RA patients may skew the T cells towards production of either IFN-γ or IL-17.
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影响因子：
4.4
作者：
Finnegan, A;Grusby, MJ;Zhang, J
通讯作者：
Zhang, J
影响因子：
4.4
作者：
Doodes, Paul D.;Cao, Yanxia;Hamel, Keith M.;Wang, Yumei;Farkas, Balint;Iwakura, Yoichiro;Finnegan, Alison
通讯作者：
Finnegan, Alison
DOI：
10.4049/jimmunol.0902907
发表时间：
2010-02-01
期刊：
Journal of immunology (Baltimore, Md. : 1950)
影响因子：
--
作者：
Doodes PD;Cao Y;Hamel KM;Wang Y;Rodeghero RL;Mikecz K;Glant TT;Iwakura Y;Finnegan A
通讯作者：
Finnegan A
影响因子：
4.4
作者：
Cruz, Andrea;Khader, Shabaana A.;Castro, Antonio G.
通讯作者：
Castro, Antonio G.
影响因子：
--
作者：
Berlo, Suzanne E.;Guichelaar, Teun;Glant, Tibor T.
通讯作者：
Glant, Tibor T.