Systemically dispersed innate IL-13-expressing cells in type 2 immunity
Systemically dispersed innate IL-13-expressing cells in type 2 immunity
复制标题
DOI：
10.1073/pnas.1003988107
复制
发表时间：
2010-06-22
影响因子：
11.1
通讯作者：
Locksley, Richard M.
中科院分区：
文献类型：
--
作者：
Price, April E.;Liang, Hong-Erh;Locksley, Richard M.
2型免疫是宿主对变应原和寄生蠕虫的一种定型反应，在很大程度上由细胞因子白细胞介素 - 4（IL - 4）和白细胞介素 - 13（IL - 13）维持。近期的研究进展使人们关注到固有细胞在启动适应性免疫中的作用，包括一种新型的谱系阴性细胞群，它能在上皮细胞因子白细胞介素 - 25（IL - 25）和白细胞介素 - 33（IL - 33）的作用下分泌白细胞介素 - 13和白细胞介素 - 5。在此，我们利用白细胞介素 - 4和白细胞介素 - 13报告基因小鼠来追踪在2型免疫过程中或在体内对白细胞介素 - 25和白细胞介素 - 33产生反应时出现的谱系阴性固有细胞。出乎意料的是，谱系阴性的白细胞介素 - 25（和白细胞介素 - 33）反应性细胞广泛分布于小鼠的组织中，在肠系膜淋巴结、脾脏和肝脏中尤为普遍。这些细胞在外源性白细胞介素 - 25或白细胞介素 - 33的作用下以及在感染巴西日圆线虫后会大量扩增，并且在这些条件下它们是主要的表达白细胞介素 - 13的固有细胞。利用白细胞介素 - 25激活这些细胞足以清除蠕虫，即使在缺乏适应性免疫的情况下也是如此。广泛分布的固有2型辅助细胞（我们将其命名为Ih2细胞）在2型免疫反应中起着不可或缺的作用。
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.