Journal
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
Volume 19, Issue 8, Pages -Publisher
MDPI
DOI: 10.3390/ijms19082261
Keywords
transforming growth factor-beta 3; transforming growth factor-beta 1; immune tolerance; regulatory T cell; autoimmune disease; immunometabolism; fibrosis
Funding
- Japan Society for the Promotion of Science
- Ministry of Education, Culture, Sports, Science and Technology of Japan [JP16K09918, JP16K15510]
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Transforming growth factor (TGF)-beta s are pluripotent cytokines with stimulatory and inhibitory properties for multiple types of immune cells. Analyses of genetic knockouts of each isoform of TGF-beta have revealed differing expression patterns and distinct roles for the three mammalian isoforms of TGF-beta. Considerable effort has been focused on understanding the molecular mechanisms of TGF-beta 1-mediated immune regulation, given its pivotal role in prohibiting systemic autoimmune disease. In recent years, functional similarities and differences between the TGF-beta isoforms have delineated their distinct roles in the development of immunopathology and immune tolerance, with increased recent attention being focused on TGF-beta 3. In addition to the characteristic properties of each TGF-beta isoform, recent progress has identified determinants of context-dependent functionality, including various cellular targets, cytokine concentrations, tissue microenvironments, and cytokine synergy, which combine to shape the physiological and pathophysiological roles of the TGF-beta s in immunity. Controlling TGF-beta production and signaling is being tested as a novel therapeutic strategy in multiple clinical trials for several human diseases. This review highlights advances in the understanding of the cellular sources, activation processes, contextual determinants, and immunological roles of TGF-beta 3 with comparisons to other TGF-beta isoforms.
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