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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. © 2022 Kim et al.


Dongeon Kim, Mingyo Kim, Tae Woo Kim, Yong-Ho Choe, Hae Sook Noh, Hyun Min Jeon, HyunSeok Kim, Youngeun Lee, Gayeong Hur, Kyung-Mi Lee, Kihyuk Shin, Sang-Il Lee, Seung-Hyo Lee. Lymph node fibroblastic reticular cells regulate differentiation and function of CD4 T cells via CD25. The Journal of experimental medicine. 2022 May 02;219(5)

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PMID: 35315876

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