PDF(Pubmed)
Abstract：
Sjögren\'s disease (SjD) is a chronic autoimmune disease characterized by focal lymphocytic inflammation in lacrimal and salivary glands. We recently identified IL-27 as a requisite signal for the spontaneous SjD-like manifestations in nonobese diabetic (NOD) mice. Here, we define T cell-intrinsic effects of IL-27 in lacrimal gland disease in NOD mice. IL-27 receptor was required by both CD4 T effector (Te) cells and CD8 T cells to mediate focal inflammation. Intrinsic IL-27 signaling was associated with PD-1 and ICOS expressing T follicular helper (Tfh)-like CD4 Te cells within lacrimal glands, including subsets defined by CD73 or CD39 expression. CD8 T cells capable of IL-27 signaling also expressed PD-1 with subsets expressing ICOS and CD73 demonstrating a T follicular cytotoxic (Tfc)-like cell phenotype and others expressing a CD39hi exhausted-like phenotype. These findings suggest IL-27 is a key early signal driving a follicular-type response in lacrimal gland inflammation in NOD mice.
摘要：
Sjögren病（SjD）是一种慢性自身免疫性疾病，其特征是泪腺和唾液腺局灶性淋巴细胞炎症。我们最近将IL-27确定为非肥胖糖尿病（NOD）小鼠自发性SjD样表现的必要信号。这里,我们定义了IL-27在NOD小鼠泪腺疾病中的T细胞内在作用。CD4T效应（Te）细胞和CD8T细胞都需要IL-27受体来介导局灶性炎症。内源性IL-27信号与泪腺内PD-1和ICOS表达T滤泡辅助性（Tfh）样CD4Te细胞相关，包括由CD73或CD39表达定义的亚群。能够进行IL-27信号传导的CD8T细胞还表达PD-1,其具有表达ICOS和CD73的亚群,表现出T滤泡细胞毒性(Tfc)样细胞表型和表达CD39hi耗尽样表型的其他细胞。这些发现表明，IL-27是NOD小鼠泪腺炎症中驱动滤泡型反应的关键早期信号。
