Graduate School of Medical Science and Engineering, Korea Advanced Institute of Science and Technology, Daejeon, South Korea.
Biomedical Science and Engineering Interdisciplinary Program, Biomedical Research Center, Korea Advanced Institute of Science and Technology, Daejeon, South Korea.
J Exp Med. 2022 May 2;219(5). doi: 10.1084/jem.20200795. Epub 2022 Mar 22.
Lymph node fibroblastic reticular cells (LN-FRCs) provide functional structure to LNs and play important roles in interactions between T cells and antigen-presenting cells. However, the direct impact of LN-FRCs on naive CD4+ T cell differentiation has not been explored. Here, we show that T cell zone FRCs of LNs (LN-TRCs) express CD25, the α chain of the IL-2 receptor heterotrimer. Moreover, LN-TRCs trans-present IL-2 to naive CD4+ T cells through CD25, thereby facilitating early IL-2-mediated signaling. CD25-deficient LN-TRCs exhibit attenuated STAT5 phosphorylation in naive CD4+ T cells during T cell differentiation, promoting T helper 17 (Th17) cell differentiation and Th17 response-related gene expression. In experimental autoimmune disease models, disease severity was elevated in mice lacking CD25 in LN-TRCs. Therefore, our results suggest that CD25 expression on LN-TRCs regulates CD4+ T cell differentiation by modulating early IL-2 signaling of neighboring, naive CD4+ T cells, influencing the overall properties of immune responses.
淋巴结纤维母细胞网状细胞 (LN-FRCs) 为淋巴结提供功能结构，并在 T 细胞与抗原呈递细胞相互作用中发挥重要作用。然而，LN-FRCs 对初始 CD4+T 细胞分化的直接影响尚未得到探索。在这里，我们表明淋巴结 T 细胞区 FRCs（LN-TRCs）表达 IL-2 受体异三聚体的 α 链 CD25。此外，LN-TRCs 通过 CD25 向初始 CD4+T 细胞转呈 IL-2，从而促进早期 IL-2 介导的信号转导。在初始 CD4+T 细胞分化过程中，缺乏 CD25 的 LN-TRCs 中 STAT5 磷酸化减弱，促进辅助性 T 细胞 17（Th17）细胞分化和 Th17 反应相关基因表达。在实验性自身免疫疾病模型中，缺乏 LN-TRCs 中 CD25 的小鼠疾病严重程度升高。因此，我们的研究结果表明，LN-TRCs 上 CD25 的表达通过调节邻近初始 CD4+T 细胞的早期 IL-2 信号，影响免疫反应的整体特性，从而调节 CD4+T 细胞分化。
