Cutting Edge: Mast Cells Express IL-17A in Rheumatoid Arthritis Synovium
Cutting Edge: Mast Cells Express IL-17A in Rheumatoid Arthritis Synovium
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DOI：
10.4049/jimmunol.0903566
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发表时间：
2010-04-01
影响因子：
4.4
通讯作者：
McInnes, Iain B.
中科院分区：
文献类型：
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作者：
Hueber, Axel J.;Asquith, Darren L.;McInnes, Iain B.
促炎细胞因子IL-17A被认为在类风湿关节炎（RA）发病过程中起着至关重要的作用。在自身免疫性关节炎的实验模型中，已经提出IL-17A的细胞来源是CD4(+) T细胞（Th17细胞）。然而，对人类炎症类风湿性关节炎组织中IL-17的来源知之甚少。我们探讨了IL-17A在人RA滑膜中的细胞来源。令人惊讶的是，只有一小部分表达il -17的细胞是T细胞，而且这些细胞是CCR6阴性的。出乎意料的是，IL-17A的大部分表达都集中在肥大细胞内。此外，我们在体外证明，肥大细胞在tnf - α、IgG复合物、C5a和LPS的刺激下产生rorc依赖性IL-17A。这些数据与IL-17A在RA发病机制中的关键作用一致，但表明除了T细胞外，特别是通过肥大细胞介导的先天免疫途径可能是IL-17A效应反应的重要组成部分。中华免疫学杂志，2010,18(4):369 - 369。
The proinflammatory cytokine IL-17A is considered a crucial player in rheumatoid arthritis (RA) pathogenesis. In experimental models of autoimmune arthritis, it has been suggested that the cellular source of IL-17A is CD4(+) T cells (Th17 cells). However, little is known about the source of IL-17 in human inflamed RA tissue. We explored the cellular sources of IL-17A in human RA synovium. Surprisingly, only a small proportion of IL-17-expressing cells were T cells, and these were CCR6 negative. Unexpectedly, the majority of IL-17A expression colocalized within mast cells. Furthermore, we demonstrated in vitro that mast cells produced RORC-dependent IL-17A upon stimulation with TNF-alpha, IgG complexes, C5a, and LPS. These data a-re consistent with a crucial role for IL-17A in RA pathogenesis but suggest that in addition to T cells innate immune pathways particularly mediated via mast cells may be an important component of the effector IL-17A response. The Journal of Immunology, 2010, 184: 3336-3340.