Regulation of the Immune Response by TGF-β: From Conception to Autoimmunity and Infection
- 1Institute of Virology and Immunology, Gladstone Institutes, San Francisco, California 94158
- 2Department of Microbiology and Immunology, University of California, San Francisco, California 94143
- 3Immunology Program, Memorial Sloan Kettering Cancer Center, New York, New York 10065
- Correspondence: shomyseh.sanjabi{at}gladstone.ucsf.edu; lim{at}mskcc.org
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↵4 These authors contributed equally to this work.
Abstract
Transforming growth factor β (TGF-β) is a pleiotropic cytokine involved in both suppressive and inflammatory immune responses. After 30 years of intense study, we have only begun to elucidate how TGF-β alters immunity under various conditions. Under steady-state conditions, TGF-β regulates thymic T-cell selection and maintains homeostasis of the naïve T-cell pool. TGF-β inhibits cytotoxic T lymphocyte (CTL), Th1-, and Th2-cell differentiation while promoting peripheral (p)Treg-, Th17-, Th9-, and Tfh-cell generation, and T-cell tissue residence in response to immune challenges. Similarly, TGF-β controls the proliferation, survival, activation, and differentiation of B cells, as well as the development and functions of innate cells, including natural killer (NK) cells, macrophages, dendritic cells, and granulocytes. Collectively, TGF-β plays a pivotal role in maintaining peripheral tolerance against self- and innocuous antigens, such as food, commensal bacteria, and fetal alloantigens, and in controlling immune responses to pathogens.
