2 型免疫中的系统性分布固有 IL-13 表达细胞。
Systemically dispersed innate IL-13-expressing cells in type 2 immunity.
机构信息
Howard Hughes Medical Institute, Department of Medicine, University of California, San Francisco, CA 94143-0795, USA.
出版信息
Proc Natl Acad Sci U S A. 2010 Jun 22;107(25):11489-94. doi: 10.1073/pnas.1003988107. Epub 2010 Jun 7.
Type 2 immunity is a stereotyped host response to allergens and parasitic helminths that is sustained in large part by the cytokines IL-4 and IL-13. Recent advances have called attention to the contributions by innate cells in initiating adaptive immunity, including a novel lineage-negative population of cells that secretes IL-13 and IL-5 in response to the epithelial cytokines IL-25 and IL-33. Here, we use IL-4 and IL-13 reporter mice to track lineage-negative innate cells that arise during type 2 immunity or in response to IL-25 and IL-33 in vivo. Unexpectedly, lineage-negative IL-25 (and IL-33) responsive cells are widely distributed in tissues of the mouse and are particularly prevalent in mesenteric lymph nodes, spleen, and liver. These cells expand robustly in response to exogenous IL-25 or IL-33 and after infection with the helminth Nippostrongylus brasiliensis, and they are the major innate IL-13-expressing cells under these conditions. Activation of these cells using IL-25 is sufficient for worm clearance, even in the absence of adaptive immunity. Widely dispersed innate type 2 helper cells, which we designate Ih2 cells, play an integral role in type 2 immune responses.
2 型免疫是一种对过敏原和寄生虫性蠕虫的定型宿主反应,在很大程度上由细胞因子 IL-4 和 IL-13 维持。最近的进展引起了人们对先天细胞在启动适应性免疫中的贡献的关注,包括一种新型的谱系阴性细胞群,其在响应上皮细胞因子 IL-25 和 IL-33 时分泌 IL-13 和 IL-5。在这里,我们使用 IL-4 和 IL-13 报告小鼠来追踪在 2 型免疫期间或在体内响应 IL-25 和 IL-33 时出现的谱系阴性先天细胞。出乎意料的是,谱系阴性的 IL-25(和 IL-33)反应性细胞广泛分布在小鼠的组织中,特别是在肠系膜淋巴结、脾脏和肝脏中。这些细胞在外源 IL-25 或 IL-33 刺激下以及感染旋毛虫 Nippostrongylus brasiliensis 后会强烈扩增,并且在这些条件下是主要的先天 IL-13 表达细胞。使用 IL-25 激活这些细胞足以清除蠕虫,即使在没有适应性免疫的情况下也是如此。广泛分散的先天 2 型辅助细胞,我们称之为 Ih2 细胞,在 2 型免疫反应中发挥着重要作用。