Tang Hui, Zhang Jie, Sun Xiuyuan, Qian Xiaoping, Zhang Yu, Jin Rong
Key Laboratory of Medical Immunology, Department of Immunology, Ministry of Health, School of Basic Medical Sciences, Peking University Health Science Center, 38 Xue Yuan Road, Beijing, China.
Sci Rep. 2016 Jul 29;6:30448. doi: 10.1038/srep30448.
IL-27, as a pleiotropic cytokine, promotes the differentiation of naïve T cells to Th1, while suppressing Th2 and Th17 differentiation in the periphery. However, the role of IL-27 in the thymocyte development remains unknown. Here we showed that IL-27 was highly expressed in thymic plasmacytoid dendritic cells (pDCs) while its receptor expression was mainly detected in CD4(+) single-positive (SP) thymocytes. Deletion of the p28 subunit in DCs resulted in a reduction of the most mature Qa-2(+) subsets of CD4(+) SP T cells. This defect was rescued by intrathymic administration of exogenous IL-27. In vitro differentiation assay further demonstrated that IL-27 alone was able to drive the maturation of the newly generated 6C10(+)CD69(+)CD4(+) SP cells into Qa-2(+) cells. Collectively, this study has revealed an important role of thymic DCs-derived IL-27 in the regulation of the phenotypic maturation of CD4(+) SP thymocytes.
白细胞介素-27(IL-27)作为一种多效性细胞因子,可促进初始T细胞向Th1细胞分化,同时在外周抑制Th2和Th17细胞分化。然而,IL-27在胸腺细胞发育中的作用尚不清楚。在此我们发现,IL-27在胸腺浆细胞样树突状细胞(pDC)中高表达,而其受体表达主要在CD4(+)单阳性(SP)胸腺细胞中检测到。DC中p28亚基的缺失导致CD4(+) SP T细胞中最成熟的Qa-2(+)亚群减少。胸腺内给予外源性IL-27可挽救这一缺陷。体外分化试验进一步证明,单独的IL-27能够促使新产生的6C10(+)CD69(+)CD4(+) SP细胞成熟为Qa-2(+)细胞。总的来说,本研究揭示了胸腺DC来源的IL-27在调节CD4(+) SP胸腺细胞表型成熟中的重要作用。