The transcription factor BATF operates as an essential differentiation checkpoint in early effector CD8+ T cells

The transcription factor BATF is required for differentiation of certain helper T cell subsets. Haining and colleagues show that BATF crucially regulates CD8 + effector cells by coordinating a transcription factor network. The transcription factor BATF is required for the differentiation of interleu...

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Vydané v:	Nature immunology Ročník 15; číslo 4; s. 373 - 383
Hlavní autori:	Kurachi, Makoto, Barnitz, R Anthony, Yosef, Nir, Odorizzi, Pamela M, DiIorio, Michael A, Lemieux, Madeleine E, Yates, Kathleen, Godec, Jernej, Klatt, Martin G, Regev, Aviv, Wherry, E John, Haining, W Nicholas
Médium:	Journal Article
Jazyk:	English
Vydavateľské údaje:	New York Nature Publishing Group US 01.04.2014 Nature Publishing Group
Predmet:	13 13/31 38 38/15 38/23 38/77 42/44 631/250/2152/1566/1571 631/250/2152/1566/1618 64/60 Animals Antigens Basic-Leucine Zipper Transcription Factors - genetics Basic-Leucine Zipper Transcription Factors - immunology Basic-Leucine Zipper Transcription Factors - metabolism Biomedicine CD8 antigen CD8-Positive T-Lymphocytes - immunology Cell differentiation Cell Differentiation - genetics Cell Growth Processes - genetics Cells, Cultured Cytokine receptors Down-Regulation Effector cells Granzyme B Granzymes - genetics Granzymes - metabolism Helper cells Immunology Infectious Diseases Inflammation Interferon regulatory factor 4 Interferon Regulatory Factors - metabolism Interferon-gamma - genetics Interferon-gamma - metabolism Interleukin 17 Lymphocyte Activation - genetics Lymphocytes Lymphocytes T Male Mice Mice, Inbred C57BL Mice, Knockout Population growth Positive Regulatory Domain I-Binding Factor 1 Proto-Oncogene Proteins c-jun - metabolism T cell receptors T-Box Domain Proteins - genetics T-Box Domain Proteins - metabolism Th17 Cells - immunology Transcription factors Transcription Factors - genetics Transcription Factors - metabolism Transcriptional Activation - genetics γ-Interferon
ISSN:	1529-2908, 1529-2916, 1529-2916
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Shrnutí:	The transcription factor BATF is required for differentiation of certain helper T cell subsets. Haining and colleagues show that BATF crucially regulates CD8 + effector cells by coordinating a transcription factor network. The transcription factor BATF is required for the differentiation of interleukin 17 (IL-17)-producing helper T cells (T H 17 cells) and follicular helper T cells (T FH cells). Here we identified a fundamental role for BATF in regulating the differentiation of effector of CD8 + T cells. BATF-deficient CD8 + T cells showed profound defects in effector population expansion and underwent proliferative and metabolic catastrophe early after encountering antigen. BATF, together with the transcription factors IRF4 and Jun proteins, bound to and promoted early expression of genes encoding lineage-specific transcription-factors (T-bet and Blimp-1) and cytokine receptors while paradoxically repressing genes encoding effector molecules (IFN-γ and granzyme B). Thus, BATF amplifies T cell antigen receptor (TCR)-dependent expression of transcription factors and augments the propagation of inflammatory signals but restrains the expression of genes encoding effector molecules. This checkpoint prevents irreversible commitment to an effector fate until a critical threshold of downstream transcriptional activity has been achieved.
Bibliografia:	ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 14 content type line 23 These authors contributed equally. M.K. and P.O. performed the experiments in the animal models; R.A.B, M.A.D., K.Y., J. G. and M.G.K. performed the gene expression and ChIP experiments; N.Y. and M.E.L. designed and performed analytic experiments; A.R., W.N.H. and E.J.W. designed the analytic experiments; W.N.H and E.J.W conceived the project; M.K., R.A.B., E.J.W. and W.N.H. wrote the paper. Author contributions
ISSN:	1529-2908 1529-2916 1529-2916
DOI:	10.1038/ni.2834