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

Kevin Man, Maria Miasari, Wei Shi, Annie Xin, Darren C. Henstridge, Simon Peter Preston, Marc Pellegrini, Gabrielle T Belz, Gordon K Smyth, Mark A Febbraio, Stephen L Nutt, Axel Kallies

Research output: Contribution to journalArticleResearchpeer-review

163 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)1155-1165
Number of pages11
JournalNature Immunology
Volume14
Issue number11
DOIs
Publication statusPublished - 2013
Externally publishedYes

Cite this

Man, Kevin ; Miasari, Maria ; Shi, Wei ; Xin, Annie ; Henstridge, Darren C. ; Preston, Simon Peter ; Pellegrini, Marc ; Belz, Gabrielle T ; Smyth, Gordon K ; Febbraio, Mark A ; Nutt, Stephen L ; Kallies, Axel. / The transcription factor IRF4 is essential for TCR affinity-mediated metabolic programming and clonal expansion of T cells. In: Nature Immunology. 2013 ; Vol. 14, No. 11. pp. 1155-1165.
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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.",
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Man, K, Miasari, M, Shi, W, Xin, A, Henstridge, DC, Preston, SP, Pellegrini, M, Belz, GT, Smyth, GK, Febbraio, MA, Nutt, SL & Kallies, A 2013, 'The transcription factor IRF4 is essential for TCR affinity-mediated metabolic programming and clonal expansion of T cells', Nature Immunology, vol. 14, no. 11, pp. 1155-1165. https://doi.org/10.1038/ni.2710

The transcription factor IRF4 is essential for TCR affinity-mediated metabolic programming and clonal expansion of T cells. / Man, Kevin; Miasari, Maria; Shi, Wei; Xin, Annie; Henstridge, Darren C.; Preston, Simon Peter; Pellegrini, Marc; Belz, Gabrielle T; Smyth, Gordon K; Febbraio, Mark A; Nutt, Stephen L; Kallies, Axel.

In: Nature Immunology, Vol. 14, No. 11, 2013, p. 1155-1165.

Research output: Contribution to journalArticleResearchpeer-review

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AU - Preston, Simon Peter

AU - Pellegrini, Marc

AU - Belz, Gabrielle T

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AU - Nutt, Stephen L

AU - Kallies, Axel

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