Stromal cells maintain immune cell homeostasis in adipose tissue via production of interleukin-33
Stromal cells maintain immune cell homeostasis in adipose tissue via production of interleukin-33
复制标题
DOI：
10.1126/sciimmunol.aax0416
复制
发表时间：
2019-05-01
影响因子：
24.8
通讯作者：
Artis, D.
中科院分区：
文献类型：
--
作者：
Mahlakoiv, T.;Flamar, A-L;Artis, D.
肥胖是由白色脂肪组织(WAT)中免疫细胞聚集和功能失调引起的慢性低度炎症引起的。白介素33(IL-33)是一种关键的细胞因子，控制着WAT中天然和获得性免疫细胞的活性和免疫稳态，尽管IL-33的来源一直存在争议。在这里，我们表明Wat居留的间充质来源的基质细胞是产生IL-33的主要来源。脂肪干细胞和前体细胞(ASPC)在所有WAT库中产生IL-33，而间皮细胞在内脏WAT中作为IL-33的额外来源。ASPC来源的IL-33通过诱导组2天然淋巴细胞衍生的2型细胞因子和维持嗜酸性粒细胞的维持，促进调节回路，维持WAT的免疫张力，而间皮细胞IL-33也在感染时通过诱导腹膜免疫反应而在WAT中起到警示作用。综上所述，这些数据揭示了组织驻留的祖细胞和先天淋巴样细胞之间先前未知的调节网络，该网络维持脂肪组织中的免疫稳态。
Obesity is driven by chronic low-grade inflammation resulting from dysregulated immune cell accumulation and function in white adipose tissue (WAT). Interleukin-33 (IL-33) is a key cytokine that controls innate and adaptive immune cell activity and immune homeostasis in WAT, although the sources of IL-33 have remained controversial. Here, we show that WAT-resident mesenchyme-derived stromal cells are the dominant producers of IL-33. Adipose stem and progenitor cells (ASPCs) produced IL-33 in all WAT depots, whereas mesothelial cells served as an additional source of IL-33 in visceral WAT. ASPC-derived IL-33 promoted a regulatory circuit that maintained an immune tone in WAT via the induction of group 2 innate lymphoid cell-derived type 2 cytokines and maintenance of eosinophils, whereas mesothelial IL-33 also acted as an alarm in by inducing peritoneal immune response upon infection. Together, these data reveal a previously unrecognized regulatory network between tissue-resident progenitor cells and innate lymphoid cells that maintains immune homeostasis in adipose tissue.