Institute of Microbiology and Hygiene, Charité - University Medicine Berlin, Berlin 12203, Germany.
Immunology Department, Genentech, Inc., South San Francisco, CA 94080, USA.
Immunity. 2015 Feb 17;42(2):321-331. doi: 10.1016/j.immuni.2015.01.011. Epub 2015 Feb 10.
T helper 1 (Th1) cell-associated immunity exacerbates ileitis induced by oral Toxoplasma gondii infection. We show here that attenuated ileitis observed in interleukin-22 (IL-22)-deficient mice was associated with reduced production of Th1-cell-promoting IL-18. IL-22 not only augmented the expression of Il18 mRNA and inactive precursor protein (proIL-18) in intestinal epithelial cells after T. gondii or Citrobacter rodentium infection, but also maintained the homeostatic amount of proIL-18 in the ileum. IL-22, however, did not induce the processing to active IL-18, suggesting a two-step regulation of IL-18 in these cells. Although IL-18 exerted pathogenic functions during ileitis triggered by T. gondii, it was required for host defense against C. rodentium. Conversely, IL-18 was required for the expression of IL-22 in innate lymphoid cells (ILCs) upon T. gondii infection. Our results define IL-18 as an IL-22 target gene in epithelial cells and describe a complex mutual regulation of both cytokines during intestinal infection.
辅助性 T 细胞 1（Th1）细胞相关免疫会加剧口服刚地弓形虫感染引起的回肠炎。我们在此表明，白细胞介素-22（IL-22）缺陷小鼠观察到的缓解性回肠炎与 Th1 细胞促进因子白细胞介素-18（IL-18）的产生减少有关。IL-22 不仅在刚地弓形虫或鼠柠檬酸杆菌感染后增强了肠上皮细胞中 Il18 mRNA 和无活性前体蛋白（proIL-18）的表达，而且还维持了回肠中 proIL-18 的稳态水平。然而，IL-22 并没有诱导 proIL-18 向活性 IL-18 的加工，这表明了这些细胞中 IL-18 的两步调节。尽管 IL-18 在刚地弓形虫引发的回肠炎中发挥了致病作用，但它对于宿主抵抗鼠柠檬酸杆菌是必需的。相反，IL-18 对于刚地弓形虫感染时固有淋巴细胞（ILCs）中 IL-22 的表达是必需的。我们的结果将 IL-18 定义为上皮细胞中 IL-22 的靶基因，并描述了这两种细胞因子在肠道感染过程中的复杂相互调节。
