Holmkvist Petra, Pool Lieneke, Hägerbrand Karin, Agace William W, Rivollier Aymeric
Immunology Section, Lund University, Lund, Sweden.
Section of Immunology and Vaccinology, National Veterinary Institute, Technical University of Denmark, Frederiksberg, Denmark.
Eur J Immunol. 2016 Jun;46(6):1371-82. doi: 10.1002/eji.201545957. Epub 2016 May 6.
IL-18 has been implicated in inflammatory bowel disease (IBD), however its role in the regulation of intestinal CD4(+) T-cell function remains unclear. Here we show that murine intestinal CD4(+) T cells express high levels of IL-18Rα and provide evidence that IL-18Rα expression is induced on these cells subsequent to their entry into the intestinal mucosa. Using the CD45RB(hi) T-cell transfer colitis model, we show that IL-18Rα is expressed on IFN-γ(+) , IL-17(+) , and IL-17(+) IFN-γ(+) effector CD4(+) T cells in the inflamed colonic lamina propria (cLP) and mesenteric lymph node (MLN) and is required for the optimal generation and/or maintenance of IFN-γ-producing cells in the cLP. In the steady state and during colitis, TCR-independent cytokine-induced IFN-γ and IL-17 production by intestinal CD4(+) T cells was largely IL-18Rα-dependent. Despite these findings however, IL-18Rα-deficient CD4(+) T cells induced comparable intestinal pathology to WT CD4(+) T cells. These findings suggest that IL-18-dependent cytokine induced activation of CD4(+) T cells is not critical for the development of T-cell-mediated colitis.
白细胞介素-18（IL-18）与炎症性肠病（IBD）有关，但其在调节肠道CD4(+) T细胞功能中的作用仍不清楚。在此我们表明，小鼠肠道CD4(+) T细胞表达高水平的IL-18Rα，并提供证据表明这些细胞进入肠道黏膜后会诱导IL-18Rα表达。利用CD45RB(hi) T细胞转移结肠炎模型，我们发现IL-18Rα在炎症性结肠固有层（cLP）和肠系膜淋巴结（MLN）中的IFN-γ(+)、IL-17(+)以及IL-17(+) IFN-γ(+)效应CD4(+) T细胞上表达，并且是cLP中产生IFN-γ的细胞最佳生成和/或维持所必需的。在稳态和结肠炎期间，肠道CD4(+) T细胞通过TCR非依赖性细胞因子诱导产生的IFN-γ和IL-17在很大程度上依赖于IL-18Rα。然而，尽管有这些发现，IL-18Rα缺陷的CD4(+) T细胞诱导的肠道病理与野生型CD4(+) T细胞相当。这些发现表明，IL-18依赖性细胞因子诱导的CD4(+) T细胞活化对于T细胞介导的结肠炎的发展并不关键。
