The transcription factor IRF4 is essential for TCR affinity-mediated metabolic programming and clonal expansion of T cells.
- Author(s)
- Man, K; Miasari, M; Shi, W; Xin, A; Henstridge, DC; Preston, S; Pellegrini, M; Belz, GT; Smyth, GK; Febbraio, MA; Nutt, SL; Kallies, A;
- Details
- Publication Year 2013-11,Volume 14,Issue #11,Page 1155-1165
- Journal Title
- Nature Immunology
- Publication Type
- Journal Article
- Abstract
- During immune responses, T cells are subject to clonal competition, which leads to the predominant expansion of high-affinity clones; however, there is little understanding of how this process is controlled. We found here that the transcription factor IRF4 was induced in a manner dependent on affinity for the T cell antigen receptor (TCR) and acted as a dose-dependent regulator of the metabolic function of activated T cells. IRF4 regulated the expression of key molecules required for the aerobic glycolysis of effector T cells and was essential for the clonal expansion and maintenance of effector function of antigen-specific CD8(+) T cells. Thus, IRF4 is an indispensable molecular 'rheostat' that 'translates' TCR affinity into the appropriate transcriptional programs that link metabolic function with the clonal selection and effector differentiation of T cells.
- Publisher
- NATURE PUBLISHING GROUP
- Research Division(s)
- Bioinformatics; Infection And Immunity; Molecular Immunology
- Publisher's Version
- https://doi.org/10.1038/ni.2710
- Terms of Use/Rights Notice
- © 2013 Nature Publishing Group, a division of Macmillan Publishers Limited. All Rights Reserved.
Creation Date: 2013-11-01 12:00:00
Last Modified: 2015-03-26 08:01:16