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The transcription factor IRF4 is essential for TCR affinity-mediated metabolic programming and clonal expansion of T cells

journal contribution
posted on 2023-05-20, 04:44 authored by Man, K, Miasari, M, Shi, W, Xin, A, Darren HenstridgeDarren Henstridge, Preston, S, Pellegrini, M, Belz, GT, Smyth, GK, Febbraio, MA, Nutt, SL, Kallies, A
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.

History

Publication title

Nature Immunology

Volume

14

Issue

11

Pagination

1155-1165

ISSN

1529-2908

Department/School

School of Health Sciences

Publisher

Nature Publishing Group

Place of publication

345 Park Ave South, New York, USA, Ny, 10010-1707

Rights statement

Copyright 2013 Springer Nature

Repository Status

  • Restricted

Socio-economic Objectives

Clinical health not elsewhere classified