Hemmers Saskia, Schizas Michail, Rudensky Alexander Y
Howard Hughes Medical Institute and Immunology Program at Sloan Kettering Institute, New York, NY.
Ludwig Center for Cancer Immunotherapy, Memorial Sloan-Kettering Cancer Center, New York, NY.
J Exp Med. 2021 Feb 1;218(2). doi: 10.1084/jem.20201234.
ST2, the receptor for the alarmin IL-33, is expressed by a subset of regulatory T (T reg) cells residing in nonlymphoid tissues, and these cells can potently expand upon provision of exogenous IL-33. Whether the accumulation and residence of T reg cells in tissues requires their cell-intrinsic expression of and signaling by ST2, or whether indirect IL-33 signaling acting on other cells suffices, has been a matter of contention. Here, we report that ST2 expression on T reg cells is largely dispensable for their accumulation and residence in nonlymphoid organs, including the visceral adipose tissue (VAT), even though cell-intrinsic sensing of IL-33 promotes type 2 cytokine production by VAT-residing T reg cells. In addition, we uncovered a novel ST2-dependent role for T reg cells in limiting the size of IL-17A-producing γδT cells in the CNS in a mouse model of neuroinflammation, experimental autoimmune encephalomyelitis (EAE). Finally, ST2 deficiency limited to T reg cells led to disease exacerbation in EAE.
警报素IL-33的受体ST2由存在于非淋巴组织中的一部分调节性T（Treg）细胞表达，并且在提供外源性IL-33时这些细胞能够有力地扩增。Treg细胞在组织中的积累和驻留是需要其细胞内在表达ST2并通过ST2进行信号传导，还是作用于其他细胞的间接IL-33信号传导就足够了，一直存在争议。在此，我们报告，Treg细胞上的ST2表达对于它们在包括内脏脂肪组织（VAT）在内的非淋巴器官中的积累和驻留基本上是不必要的，尽管IL-33的细胞内在感知促进了驻留在VAT中的Treg细胞产生2型细胞因子。此外，在神经炎症的小鼠模型实验性自身免疫性脑脊髓炎（EAE）中，我们发现Treg细胞在限制中枢神经系统中产生IL-17A的γδT细胞的大小方面具有一种新的依赖于ST2的作用。最后，仅限于Treg细胞的ST2缺陷导致EAE疾病加重。
