期刊
EUROPEAN JOURNAL OF IMMUNOLOGY
卷 43, 期 11, 页码 2818-2823出版社
WILEY
DOI: 10.1002/eji.201343689
关键词
EAE; T-bet; T cells; Th1; Th17
类别
资金
- UK Medical Research Council
- Wellcome Trust
- MRC [G0801924, G1100084, G0901697] Funding Source: UKRI
- Medical Research Council [G0901697, G1100084, G0801924] Funding Source: researchfish
T cells that produce both IL-17 and IFN-, and co-express ROR-t and T-bet, are often found at sites of autoimmune inflammation. However, it is unknown whether this co-expression of T-bet with ROR-t is a prerequisite for immunopathology. We show here that T-bet is not required for the development of Th17-driven experimental autoimmune encephalomyelitis (EAE). The disease was not impaired in T-bet(-/-) mice and was associated with low IFN- production and elevated IL-17 production among central nervous system (CNS) infiltrating CD4(+) T cells. T-bet(-/-) Th17 cells generated in the presence of IL-6/TGF-/IL-1 and IL-23 produced GM-CSF and high levels of IL-17 and induced disease upon transfer to naive mice. Unlike their WT counterparts, these T-bet(-/-) Th17 cells did not exhibit an IL-17IFN- switch upon reencounter with antigen in the CNS, indicating that this functional change is not critical to disease development. In contrast, T-bet was absolutely required for the pathogenicity of myelin-responsive Th1 cells. T-bet-deficient Th1 cells failed to accumulate in the CNS upon transfer, despite being able to produce GM-CSF. Therefore, T-bet is essential for establishing Th1-mediated inflammation but is not required to drive IL-23-induced GM-CSF production, or Th17-mediated autoimmune inflammation.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据