| Literature DB >> 26950239 |
Annie Xin1,2, Frederick Masson1,2, Yang Liao1,2, Simon Preston1,2, Tianxia Guan3, Renee Gloury1,2, Moshe Olshansky1,4, Jian-Xin Lin5, Peng Li5, Terence P Speed1,6, Gordon K Smyth1,6, Matthias Ernst1,2, Warren J Leonard5, Marc Pellegrini1,2, Susan M Kaech4,7, Stephen L Nutt1,2, Wei Shi1,6, Gabrielle T Belz1,2, Axel Kallies1,2.
Abstract
T cell responses are guided by cytokines that induce transcriptional regulators, which ultimately control differentiation of effector and memory T cells. However, it is unknown how the activities of these molecular regulators are coordinated and integrated during the differentiation process. Using genetic approaches and transcriptional profiling of antigen-specific CD8(+) T cells, we reveal a common program of effector differentiation that is regulated by IL-2 and IL-12 signaling and the combined activities of the transcriptional regulators Blimp-1 and T-bet. The loss of both T-bet and Blimp-1 leads to abrogated cytotoxic function and ectopic IL-17 production in CD8(+) T cells. Overall, our data reveal two major overlapping pathways of effector differentiation governed by the availability of Blimp-1 and T-bet and suggest a model for cytokine-induced transcriptional changes that combine, quantitatively and qualitatively, to promote robust effector CD8(+) T cell differentiation.Entities:
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Year: 2016 PMID： 26950239 PMCID： PMC5779087 DOI： 10.1038/ni.3410
Source DB: PubMed Journal: Nat Immunol ISSN： 1529-2908 Impact factor: 25.606