IL-23R+ innate lymphoid cells induce colitis via interleukin-22-dependent mechanism.
IL-23R+ innate lymphoid cells induce colitis via interleukin-22-dependent mechanism.
复制标题
IL-23R+先天淋巴样细胞通过白介素-22依赖性机制诱导结肠炎。
作者：
白细胞介素（IL）-23 R和信号传导成分的多态性与包括炎症性肠病（IBD）在内的多种自身免疫性疾病相关。与辅助性T细胞17型（Th 17）谱系相似，3型先天性淋巴样细胞（ILC）表达视黄酸相关孤儿受体γt（Rorγt）和IL-23 R，因此产生Th 17型细胞因子。最近的报道涉及IBD中的3型ILC;然而，这些细胞中的IL-23 R信号传导如何促成发病机制尚不清楚。据报道，由3型ILC大量产生的IL-22在适应性结肠炎模型中具有有益作用和致病作用，但在先天性结肠炎模型中仅具有保护作用。在此，通过在Rag 1 −/−小鼠中采用慢性CD 45 RB高CD 4 + T细胞转移和抗CD 40抗体诱导的急性先天性结肠炎模型，我们证明了IL-23 R在结肠炎发生中的相反作用：前者是保护性的，而后者是致病性的。此外，我们表明IL-23 R信号通过IL-22促进先天性结肠炎，因为IL-22的中和保护小鼠免受结肠炎，并且将IL-22加回IL-23 R缺陷动物恢复疾病。总的来说，我们的研究结果表明，类似于其在慢性或适应性结肠炎中的有争议的作用，IL-22也可能在先天性结肠炎发病机制中以背景和侮辱依赖的方式发挥相反的作用。
Polymorphisms of interleukin (IL)-23R and signaling components are associated with several autoimmune diseases, including inflammatory bowel diseases (IBD). Similar to T helper type 17 (Th17) lineage, type 3 innate lymphoid cells (ILCs) express retinoic acid–related orphan receptor γt (Rorγt) and IL-23R and hence, produce Th17-type cytokines. Recent reports implicated type 3 ILCs in IBD; however, how IL-23R signaling in these cells contributes to pathogenesis is unknown. IL-22, produced in copious amounts by type 3 ILCs, was reported to have both beneficial and pathogenic effects in adaptive, yet only a protective role in innate colitis models. Herein, by employing chronic CD45RBhigh CD4+ T-cell transfer and anti-CD40 antibody-induced acute innate colitis models in Rag1−/− mice, wedemonstrated opposite roles for IL-23R in colitogenesis: in the former a protective, and in the latter a pathogenic role. Furthermore, we show that IL-23R signaling promotes innate colitis via IL-22 as neutralization of IL-22 protected mice from colitis and adding back of IL-22 to IL-23R-deficient animals restored the disease. Collectively, our results reveal that similar to its controversial role during chronic or adaptive colitis, IL-22 may also have opposite roles in innate colitis pathogenesis in a context and insult-dependent manner.
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