Li Hao, Hsu Hui-Chen, Wu Qi, Yang PingAr, Li Jun, Luo Bao, Oukka Mohamed, Steele Claude H, Cua Daniel J, Grizzle William E, Mountz John D
1] Division of Clinical Immunology & Rheumatology, Department of Medicine, University of Alabama at Birmingham, Birmingham, Alabama 35294, USA [2] Department Microbiology, University of Alabama at Birmingham, Birmingham, Alabama 35294, USA.
Division of Clinical Immunology & Rheumatology, Department of Medicine, University of Alabama at Birmingham, Birmingham, Alabama 35294, USA.
Nat Commun. 2014 Jul 8;5:4259. doi: 10.1038/ncomms5259.
Transient thymic involution is frequently found during inflammation, yet the mode of action of inflammatory cytokines is not well defined. Here we report that interleukin-23 (IL-23) production by the thymic dendritic cells (DCs) promotes apoptosis of the CD4(hi)CD8(hi) double-positive (DP) thymocytes. A deficiency in IL-23 signalling interferes with negative selection in the male D(b)/H-Y T-cell receptor (TCR) transgenic mice. IL-23 plus TCR signalling results in significant upregulation of IL-23 receptor (IL-23R) expressed predominantly on CD4(hi)CD8(hi)CD3(+)αβTCR(+) DP thymocytes, and leads to RORγt-dependent apoptosis. These results extend the action of IL-23 beyond its peripheral effects to a unique role in TCR-mediated negative selection including elimination of natural T regulatory cells in the thymus.
炎症期间经常会出现短暂性胸腺退化，然而炎性细胞因子的作用模式尚未明确。在此我们报告，胸腺树突状细胞（DC）产生的白细胞介素-23（IL-23）可促进CD4(hi)CD8(hi)双阳性（DP）胸腺细胞凋亡。IL-23信号传导缺陷会干扰雄性D(b)/H-Y T细胞受体（TCR）转基因小鼠的阴性选择。IL-23加TCR信号传导会导致主要在CD4(hi)CD8(hi)CD3(+)αβTCR(+) DP胸腺细胞上表达的IL-23受体（IL-23R）显著上调，并导致RORγt依赖性凋亡。这些结果将IL-23的作用从其外周效应扩展到TCR介导的阴性选择中的独特作用，包括消除胸腺中的天然调节性T细胞。
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