外膜基质细胞定义了 2 类固有淋巴细胞组织龛。
Adventitial Stromal Cells Define Group 2 Innate Lymphoid Cell Tissue Niches.
机构信息
Department of Laboratory Medicine, University of California, San Francisco, San Francisco, CA 94143, USA.
Department of Otolaryngology-Head and Neck Surgery, University of California, San Francisco, San Francisco, CA 94143, USA.
出版信息
Immunity. 2019 Mar 19;50(3):707-722.e6. doi: 10.1016/j.immuni.2019.02.002. Epub 2019 Feb 26.
Type 2 lymphocytes promote both physiologic tissue remodeling and allergic pathology, yet their physical tissue niches are poorly described. Here, we used quantitative imaging to define the tissue niches of group 2 innate lymphoid cells (ILC2s), which are critical instigators of type 2 immunity. We identified a dominant adventitial niche around lung bronchi and larger vessels in multiple tissues, where ILC2s localized with subsets of dendritic and regulatory T cells. However, ILC2s were most intimately associated with adventitial stromal cells (ASCs), a mesenchymal fibroblast-like subset that expresses interleukin-33 (IL-33) and thymic stromal lymphopoietin (TSLP). In vitro, ASCs produced TSLP that supported ILC2 accumulation and activation. ILC2s and IL-13 drove reciprocal ASC expansion and IL-33 expression. During helminth infection, ASC depletion impaired lung ILC2 and Th2 cell accumulation and function, which are in part dependent on ASC-derived IL-33. These data indicate that adventitial niches are conserved sites where ASCs regulate type 2 lymphocyte expansion and function.
2 型淋巴细胞既能促进生理性组织重塑，也能促进过敏病理过程，但它们的组织栖息龛尚未被充分描述。在这里，我们使用定量成像技术来定义 2 型固有淋巴细胞（ILC2）的组织栖息龛，ILC2 是 2 型免疫的关键启动子。我们在多个组织中发现了肺支气管和较大血管周围的主导性外膜龛，ILC2 与树突状细胞和调节性 T 细胞的亚群定位于此处。然而，ILC2 与外膜基质细胞（ASC）最为密切相关，ASC 是一种表达白细胞介素 33（IL-33）和胸腺基质淋巴细胞生成素（TSLP）的间充质成纤维细胞样亚群。在体外，ASC 产生 TSLP，支持 ILC2 的积累和激活。ILC2 和 IL-13 驱动 ASC 的扩张和 IL-33 的表达。在寄生虫感染期间，ASC 耗竭会损害肺 ILC2 和 Th2 细胞的积累和功能，而这在一定程度上依赖于 ASC 衍生的 IL-33。这些数据表明，外膜龛是 ASC 调节 2 型淋巴细胞扩增和功能的保守部位。
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