Coquet Jonathan M, Chakravarti Sumone, Smyth Mark J, Godfrey Dale I
Department of Microbiology and Immunology, University of Melbourne, Parkville, Victoria, Australia.
J Immunol. 2008 Jun 1;180(11):7097-101. doi: 10.4049/jimmunol.180.11.7097.
Recent studies have suggested that IL-21 is a key factor in the development of IL-17-producing CD4 T cells (Th17) and that the induction of experimental autoimmune encephalomyelitis, which depends on mounting an efficient Th17 response, is reportedly impaired in the absence of IL-21 signaling. In this study, we provide supportive in vitro evidence that IL-21 can drive Th17 responses in conjunction with TGF-beta. However, more importantly we also demonstrate, using IL-21- and IL-21R-deficient mice, that IL-21 is not essential for the differentiation of Th17 cells in vitro and in vivo. Moreover, we show that IL-21- and IL-21R-deficient mice are highly susceptible to experimental autoimmune encephalomyelitis with disease scores that were comparable, or even higher at the peak of disease, to those of control mice. Thus, our results challenge the notion that IL-21 is a key factor in driving Th17 immunity and disease.
最近的研究表明，白细胞介素-21（IL-21）是产生白细胞介素-17的CD4 T细胞（Th17）发育的关键因素，并且据报道，在缺乏IL-21信号传导的情况下，依赖于有效Th17反应的实验性自身免疫性脑脊髓炎的诱导会受损。在本研究中，我们提供了体外支持性证据，表明IL-21可与转化生长因子-β（TGF-β）共同驱动Th17反应。然而，更重要的是，我们还使用IL-21和IL-21R缺陷小鼠证明，IL-21在体外和体内对Th17细胞的分化并非必不可少。此外，我们表明，IL-21和IL-21R缺陷小鼠对实验性自身免疫性脑脊髓炎高度敏感，其疾病评分在疾病高峰期与对照小鼠相当，甚至更高。因此，我们的结果挑战了IL-21是驱动Th17免疫和疾病的关键因素这一观点。
