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Article Abstract

Regulatory T cells (T) have diverse functional specification in homeostasis and disease. However, how liver T function and are transcriptionally regulated in obesity is not well understood. Here, we identified that effector T expressing activating transcription factor 4 (ATF4) were enriched in the livers of obese mice. ATF4 was critical for driving an effector T transcriptional program, and ATF4-expressing T promoted the development of obesity-induced liver fibrosis by enhancing transforming growth factor-β activation via integrin αvβ8. T-specific deletion of resulted in reduced liver T and attenuation of obesity-induced liver abnormalities. Furthermore, ATF4 was required to promote the differentiation of nonlymphoid tissue T precursors under steady state. These findings demonstrate that ATF4 is important for regulating T functional specification in homeostasis and obesity.

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http://dx.doi.org/10.1126/sciimmunol.adp7193DOI Listing

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