Divergent Roles of Interferon-γ and Innate Lymphoid Cells in Innate and Adaptive Immune Cell-Mediated Intestinal Inflammation.
Divergent Roles of Interferon-γ and Innate Lymphoid Cells in Innate and Adaptive Immune Cell-Mediated Intestinal Inflammation.
复制标题
干扰素-γ和先天淋巴样细胞在先天和适应性免疫细胞介导的肠炎中的作用。
DOI：
10.3389/fimmu.2018.00023
复制
发表时间：
2018
影响因子：
7.3
通讯作者：
Mueller C
中科院分区：
文献类型：
--
作者：
Brasseit J;Kwong Chung CKC;Noti M;Zysset D;Hoheisel-Dickgreber N;Genitsch V;Corazza N;Mueller C
干扰素γ（IFNγ）的异常表达与许多自身免疫性和炎症性疾病（包括炎症性肠病（IBD））的发病机制相关。然而，IFNγ在慢性肠道炎症发病机制中的需求仍然存在争议。因此，本研究的目的是研究IFNγ在使用遗传和微生物群稳定宿主的先天性和适应性免疫细胞介导的肠道炎症实验小鼠模型中的作用。虽然我们发现IFNγ以先天性淋巴细胞（ILC）依赖性方式驱动抗CD 40结肠炎模型中的急性肠道炎症，但由转移的CD 4 T细胞和/或淋巴细胞减少Rag 1 −/−受体小鼠的细胞分泌的IFNγ对CD 4 T细胞介导的结肠炎无效。在不存在IFNγ的情况下，CD 4 T细胞受体小鼠中的肠道炎症与增强的IL 17应答相关;因此，靶向IFNγ缺陷小鼠中的IL 17信号传导减少了T细胞介导的结肠炎。有趣的是，与抗CD 40结肠炎模型相反，在致结肠炎性CD 4 T细胞的Rag 1 −/−受体中，ILC的消耗并不能阻止结肠炎症的诱导。总之，我们的研究结果表明，IFNγ是诱导肠道炎症的一种必需或多余的促炎细胞因子，这取决于所用的实验小鼠模型和所涉及的诱导免疫细胞群的关键疾病的性质。
Aberrant interferon gamma (IFNγ) expression is associated with the pathogenesis of numerous autoimmune- and inflammatory disorders, including inflammatory bowel diseases (IBD). However, the requirement of IFNγ for the pathogenesis of chronic intestinal inflammation remains controversial. The aim of this study was thus to investigate the role of IFNγ in experimental mouse models of innate and adaptive immune cell-mediated intestinal inflammation using genetically and microbiota-stabilized hosts. While we find that IFNγ drives acute intestinal inflammation in the anti-CD40 colitis model in an innate lymphoid cell (ILC)-dependent manner, IFNγ secreted by both transferred CD4 T cells and/or cells of the lymphopenic Rag1−/− recipient mice was dispensable for CD4 T cell-mediated colitis. In the absence of IFNγ, intestinal inflammation in CD4 T cell recipient mice was associated with enhanced IL17 responses; consequently, targeting IL17 signaling in IFNγ-deficient mice reduced T cell-mediated colitis. Intriguingly, in contrast to the anti-CD40 model of colitis, depletion of ILC in the Rag1−/− recipients of colitogenic CD4 T cells did not prevent induction of colonic inflammation. Together, our findings demonstrate that IFNγ represents an essential, or a redundant, pro-inflammatory cytokine for the induction of intestinal inflammation, depending on the experimental mouse model used and on the nature of the critical disease inducing immune cell populations involved.