Lymph node fibroblastic reticular cells regulate differentiation and function of CD4 T cells via CD25

Dongeon Kim, Mingyo Kim, Tae Woo Kim, Yong Ho Choe, Hae Sook Noh, Hyun Min Jeon, Hyun Seok Kim, Youngeun Lee, Gayeong Hur, Kyung Mi Lee, Kihyuk Shin, Sang Il Lee, Seung Hyo Lee

Research output: Contribution to journalArticlepeer-review

Abstract

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.

Original languageEnglish
JournalJournal of Experimental Medicine
Volume219
Issue number5
DOIs
Publication statusPublished - 2022 May 2

ASJC Scopus subject areas

  • Medicine(all)

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