RRC ID 75010
Author Read KA, Jones DM, Pokhrel S, Hales EDS, Varkey A, Tuazon JA, Eisele CD, Abdouni O, Saadey A, Leonard MR, Warren RT, Powell MD, Boss JM, Hemann EA, Yount JS, Xin G, Ghoneim HE, Lio CJ, Freud AG, Collins PL, Oestreich KJ.
Title Aiolos represses CD4+ T cell cytotoxic programming via reciprocal regulation of TFH transcription factors and IL-2 sensitivity.
Journal Nat Commun
Abstract During intracellular infection, T follicular helper (TFH) and T helper 1 (TH1) cells promote humoral and cell-mediated responses, respectively. Another subset, CD4-cytotoxic T lymphocytes (CD4-CTLs), eliminate infected cells via functions typically associated with CD8+ T cells. The mechanisms underlying differentiation of these populations are incompletely understood. Here, we identify the transcription factor Aiolos as a reciprocal regulator of TFH and CD4-CTL programming. We find that Aiolos deficiency results in downregulation of key TFH transcription factors, and consequently reduced TFH differentiation and antibody production, during influenza virus infection. Conversely, CD4-CTL programming is elevated, including enhanced Eomes and cytolytic molecule expression. We further demonstrate that Aiolos deficiency allows for enhanced IL-2 sensitivity and increased STAT5 association with CD4-CTL gene targets, including Eomes, effector molecules, and IL2Ra. Thus, our collective findings identify Aiolos as a pivotal regulator of CD4-CTL and TFH programming and highlight its potential as a target for manipulating CD4+ T cell responses.
Volume 14(1)
Pages 1652
Published 2023-3-24
DOI 10.1038/s41467-023-37420-0
PII 10.1038/s41467-023-37420-0
PMID 36964178
PMC PMC10039023
MeSH CD4-Positive T-Lymphocytes CD8-Positive T-Lymphocytes Cell Differentiation Interleukin-2 / genetics Interleukin-2 / metabolism T-Lymphocytes, Helper-Inducer* Transcription Factors* / genetics Transcription Factors* / metabolism
IF 12.121
Mice RBRC05582