The transcription factors T-bet and GATA-3 control alternative pathways of T-cell differentiation through a shared set of target genes
Richard G. Jenner,Michael J. Townsend,Ian Jackson,Kaiming Sun,Russell D. Bouwman,Richard A. Young,Laurie H. Glimcher,Graham M. Lord +7 more
TLDR
Data show that the choice between Th1 and Th2 lineage commitment is the result of the opposing action of T-bet and GATA-3 at a shared set of target genes and may provide a general paradigm for the interaction of lineage-specifying transcription factors.Abstract:
Upon detection of antigen, CD4+ T helper (Th) cells can differentiate into a number of effector types that tailor the immune response to different pathogens Alternative Th1 and Th2 cell fates are specified by the transcription factors T-bet and GATA-3, respectively Only a handful of target genes are known for these two factors and because of this, the mechanism through which T-bet and GATA-3 induce differentiation toward alternative cell fates is not fully understood Here, we provide a genomic map of T-bet and GATA-3 binding in primary human T cells and identify their target genes, most of which are previously unknown In Th1 cells, T-bet associates with genes of diverse function, including those with roles in transcriptional regulation, chemotaxis and adhesion GATA-3 occupies genes in both Th1 and Th2 cells and, unexpectedly, shares a large proportion of targets with T-bet Re-complementation of T-bet alters the expression of these genes in a manner that mirrors their differential expression between Th1 and Th2 lineages These data show that the choice between Th1 and Th2 lineage commitment is the result of the opposing action of T-bet and GATA-3 at a shared set of target genes and may provide a general paradigm for the interaction of lineage-specifying transcription factorsread more
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Transcription factor T-bet represses expression of the inhibitory receptor PD-1 and sustains virus-specific CD8 + T cell responses during chronic infection
Charlly Kao,Kenneth J. Oestreich,Michael A. Paley,Alison Crawford,Jill M. Angelosanto,Mohammed Alkhatim A. Ali,Andrew M. Intlekofer,Jeremy M. Boss,Steven L. Reiner,Amy S. Weinmann,E. John Wherry +10 more
TL;DR: It is demonstrated that the transcription factor T-bet regulated the exhaustion of CD8+ T cells and the expression of inhibitory receptors and suggested therapeutic opportunities involving higher T-Bet expression during chronic infection.
Journal ArticleDOI
T-bet: a bridge between innate and adaptive immunity.
TL;DR: T-bet has a fundamental role in coordinating type 1 immune responses by controlling a network of genetic programmes that regulate the development of certain immune cells and the effector functions of others.
Journal ArticleDOI
T-bet represses T(H)17 differentiation by preventing Runx1-mediated activation of the gene encoding RORγt
Vanja Lazarevic,Xi Chen,Jae-Hyuck Shim,Eun Sook Hwang,Eun Jung Jang,Alexandra N. Bolm,Mohamed Oukka,Vijay K. Kuchroo,Laurie H. Glimcher +8 more
TL;DR: The transcription factor T-bet suppressed development of the TH17 cell lineage by inhibiting transcription of Rorc (which encodes the transcription factor RORγt), reinforcing the idea of master regulators that shape immune responses by simultaneously activating one genetic program while silencing the activity of competing regulators in a common progenitor cell.
Journal ArticleDOI
Roles of IFN-γ in tumor progression and regression: a review.
TL;DR: The current knowledge concerning the roles of IFN-γ in the TME as a part of the complex immune response to cancer is discussed and the importance of identifying IFn-γ responsive patients to improve their sensitivity to immuno-therapies is highlighted.
Journal ArticleDOI
The Transcription Factor T-bet Regulates Intestinal Inflammation Mediated by Interleukin-7 Receptor+ Innate Lymphoid Cells
Nick Powell,Nick Powell,Nick Powell,Alan W. Walker,Emilie Stolarczyk,James B. Canavan,James B. Canavan,James B. Canavan,M. Refik Gökmen,Ellen Marks,Ellen Marks,Ian Jackson,Ian Jackson,Ahmed Hashim,Michael A. Curtis,Richard G. Jenner,Jane K. Howard,Julian Parkhill,Thomas T. MacDonald,Graham M. Lord,Graham M. Lord +20 more
TL;DR: The mechanism by which T-bet regulates the complex interplay between mucosal dendritic cells, ILCs, and the intestinal microbiota is demonstrated, as well as Helicobacter typhlonius as a key disease trigger driving excess TNF-α production and promoting colitis in TRUC mice.
References
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