脂肪间充质基质细胞通过IL-33驱动的ST2调节性T细胞扩增抑制实验性干燥综合征。

Adipose-mesenchymal stromal cells suppress experimental Sjögren syndrome by IL-33-driven expansion of ST2 regulatory T cells.

作者信息

Liu Ousheng, Xu Junji, Wang Fu, Jin Wenwen, Zanvit Peter, Wang Dandan, Goldberg Nathan, Cain Alexander, Guo Nancy, Han Yichen, Bynum Andrew, Ma Guowu, Wang Songlin, Tang Zhangui, Chen Wanjun

机构信息

Mucosal Immunology Section, NIDCR, NIH, Bethesda, MD 20892, USA.

Hunan Key Laboratory of Oral Health Research & Hunan 3D Printing Engineering Research Center of Oral Care & Hunan Clinical Research Center of Oral Major Diseases and Oral Health & Xiangya Stomatological Hospital & Xiangya School of Stomatology, Central South University, Changsha 410008, China.

出版信息

iScience. 2021 Apr 16;24(5):102446. doi: 10.1016/j.isci.2021.102446. eCollection 2021 May 21.

Adipose-derived mesenchymal stromal cells (ADSCs) play important roles in the alleviation of inflammation and autoimmune diseases. Interleukin-33 (IL-33), a member of the IL-1 family, has been shown to regulate innate and adaptive immunity. However, it is still unknown whether ADSCs regulate immune responses via IL-33. We show here that ADSCs produced IL-33 in response to IL-1β stimulation, which depended on TAK1, ERK, and p38 pathways. ADSCs-derived IL-33 drove the proliferation of CD4Foxp3ST2 regulatory T cells (Tregs) and alleviated experimental autoimmune Sjögren syndrome in mice. Importantly, human ADSCs also produced IL-33 in response to IL-1β. Thus, we have revealed a previously unrecognized immunoregulatory function of ADSCs by IL-33 production in experimental autoimmunity, which may have clinical applications for human immunopathology.

脂肪来源的间充质基质细胞（ADSCs）在减轻炎症和自身免疫性疾病方面发挥着重要作用。白细胞介素-33（IL-33）是IL-1家族的成员，已被证明可调节先天性和适应性免疫。然而，ADSCs是否通过IL-33调节免疫反应仍不清楚。我们在此表明，ADSCs在受到IL-1β刺激时会产生IL-33，这依赖于TAK1、ERK和p38信号通路。ADSCs衍生的IL-33促进了CD4Foxp3ST2调节性T细胞（Tregs）的增殖，并减轻了小鼠实验性自身免疫性干燥综合征。重要的是，人ADSCs在受到IL-1β刺激时也会产生IL-33。因此，我们通过在实验性自身免疫中产生IL-33揭示了ADSCs以前未被认识的免疫调节功能，这可能对人类免疫病理学具有临床应用价值。