Phenotypic differences between Th1 and Th17 cells and negative regulation of Th1 cell differentiation by IL-17
Phenotypic differences between Th1 and Th17 cells and negative regulation of Th1 cell differentiation by IL-17
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DOI：
10.1189/jlb.1006610
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发表时间：
2007-05-01
影响因子：
5.5
通讯作者：
Galli, Stephen J.
中科院分区：
文献类型：
--
作者：
Nakae, Susumu;Iwakura, Yoichiro;Galli, Stephen J.
最近来自几个小组的证据表明，产生il -17的Th17细胞，而不是曾经认为的产生ifn - γ的Th1细胞，可以代表诱导/发展几种自身免疫性和过敏性疾病的关键效应细胞。尽管Th17细胞与Th1细胞表现出一定的表型和发育差异，但这两种T细胞亚群之间的差异程度仍未完全了解。我们发现细胞表面分子在Th17细胞上的表达谱与Th1细胞比Th2细胞更相似。然而，虽然某些Th1谱系标记物[如IL-18受体α、CXCR3和T细胞Ig结构域、黏蛋白样结构域3 (mucin-like domain-3, TIM-3)]在Th17细胞上表达，但不表达th2谱系标记物（如T1/ST2、TIM-1和TIM-2），但在Th17和Th1细胞间表达强度不同。此外，CTLA-1、ICOS、程序性死亡配体1、CD153、Fas和tnf相关激活诱导的细胞因子在Th17细胞上的表达高于Th1细胞。我们发现IL-23或IL-17在外源IL-12存在的情况下可以抑制Th1细胞的分化。我们还证实IL-12或ifn - γ可以负向调节Th17细胞的分化。然而，在没有APC的情况下，这些细胞因子不能调节对T细胞分化的影响。
Recent evidence from several groups indicates that IL-17-producing Th17 cells, rather than, as once was thought, IFN-gamma-producing Th1 cells, can represent the key effector cells in the induction/development of several autoimmune and allergic disorders. Although Th17 cells exhibit certain phenotypic and developmental differences from Th1 cells, the extent of the differences between these two T cell subsets is still not fully understood. We found that the expression profile of cell surface molecules on Th17 cells has more similarities to that of Th1 cells than Th2 cells. However, although certain Th1-lineage markers [i.e., IL-18 receptor alpha, CXCR3, and T cell Ig domain, mucin-like domain-3 (TIM-3)], but not Th2-lineage markers (i.e., T1/ST2, TIM-1, and TIM-2), were expressed on Th17 cells, the intensity of expression was different between Th17 and Th1 cells. Moreover, the expression of CTLA-1, ICOS, programmed death ligand 1, CD153, Fas, and TNF-related activation-induced cytokine was greater on Th17 cells than on Th1 cells. We found that IL-23 or IL-17 can suppress Th1 cell differentiation in the presence of exogenous IL-12 in vitro. We also confirmed that IL-12 or IFN-gamma can negatively regulate Th17 cell differentiation. However, these cytokines could not modulate such effects on T cell differentiation in the absence of APC.