CD45RA+ 调节性 T 细胞与 TNF-α 在调控人类 Th17 分化中的相互作用。
Interplay between CD45RA+ regulatory T cells and TNF-alpha in the regulation of human Th17 differentiation.
机构信息
Immunoregulation Laboratory, Centre de Recherche du Centre Hospitalier de l'Université de Montréal (CRCHUM), University of Montreal, Montreal, Quebec, Canada.
出版信息
Int Immunol. 2010 Apr;22(4):237-44. doi: 10.1093/intimm/dxp130. Epub 2010 Feb 24.
The balance between effector CD4(+) T cells secreting IL-17 (T(h)17) and regulatory T cells (Treg) plays an important role in autoimmune disorders that include rheumatoid arthritis (RA) and Crohn's disease. Tumor necrosis factor (TNF)-alpha is a key pro-inflammatory cytokine that contributes to disease pathogenesis. We investigated the interplay between CD45RA(+) Treg and TNF-alpha in the regulation of human T(h)17 differentiation. We found that CD45RA(+) Treg promoted while TNF-alpha inhibited naive CD4(+) T-cell differentiation into IL-17 and CCL20 co-expressing T(h)17 cells without influencing their IL-22 release. Unexpectedly, CD45RA(+) Treg depletion abrogated TNF-alpha suppressive function. Finally, dendritic cell-derived TNF-alpha suppressed the development of IL-17(+)CCL20(+) expressing T(h)17 cells. In conclusion, CD45RA(+) Treg positively governs human T(h)17 development, which is impaired by TNF-alpha. We propose that TNF-alpha may represent a negative feedback mechanism to control IL-17/CCL20- but not IL-22-associated autoimmune pathologies.
效应性 CD4(+)T 细胞分泌白细胞介素 17（Th17）与调节性 T 细胞（Treg）之间的平衡在包括类风湿关节炎（RA）和克罗恩病（Crohn's disease）在内的自身免疫性疾病中发挥着重要作用。肿瘤坏死因子（TNF）-α是一种关键的促炎细胞因子，有助于疾病的发病机制。我们研究了 CD45RA(+)Treg 与 TNF-α在调节人类 Th17 分化中的相互作用。我们发现 CD45RA(+)Treg 促进而 TNF-α抑制初始 CD4(+)T 细胞分化为同时表达白细胞介素 17 和 CCL20 的 Th17 细胞，而不影响其释放白细胞介素 22。出乎意料的是，CD45RA(+)Treg 的耗竭消除了 TNF-α的抑制作用。最后，树突状细胞衍生的 TNF-α抑制了表达白细胞介素 17(+)CCL20(+)的 Th17 细胞的发育。总之，CD45RA(+)Treg 正向调控人类 Th17 的发育，而 TNF-α则损害了这一过程。我们提出 TNF-α可能代表一种负反馈机制，以控制与白细胞介素 17/CCL20 相关但与白细胞介素 22 无关的自身免疫性病理。
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