Journal
IMMUNITY
Volume 28, Issue 6, Pages 763-773Publisher
CELL PRESS
DOI: 10.1016/j.immuni.2008.04.016
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Funding
- NATIONAL INSTITUTE OF ALLERGY AND INFECTIOUS DISEASES [R01AI037584, R01AI046564, R01AI084987] Funding Source: NIH RePORTER
- NATIONAL INSTITUTE OF DIABETES AND DIGESTIVE AND KIDNEY DISEASES [P30DK032520] Funding Source: NIH RePORTER
- NIAID NIH HHS [AI37584, R01 AI037584, R01 AI046564, R01 AI046564-07, R01 AI084987, AI46564, R01 AI046564-08, R01 AI046564-06A2] Funding Source: Medline
- NIDDK NIH HHS [P30 DK032520, DK32520] Funding Source: Medline
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Differentiation of naive CD4(+) T cells into T helper type 1 (Th1) effector cells requires both T cell receptor (TCR) signaling and cytokines such as interleukin-12 and interferon gamma (IFN-gamma). Here, we report that a third cytokine signal, mediated by the Janus family tyrosine kinase 3 (Jak3) and signal transducer and activator of transcription 5 (STAT5) pathway, is also required for Th1 cell differentiation. In the absence of Jak3-dependent signals, naive CD4(+) T cells proliferate robustly but produce little IFN-gamma after Th1 cell polarization in vitro. This defect is not due to reduced activation of STAT1 or STAT4 or to impaired upregulation of the transcription factor T-bet. Instead, we find that T-bet binding to the Ifng promoter is greatly diminished in the absence of Jak3-dependent signals, correlating with a decrease in Ifng promoter accessibility and histone acetylation. These data indicate that Jak3 regulates epigenetic modification and chromatin remodeling of the Ifng locus during Th1 cell differentiation.
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