2. Academic Validation
  3. Reevaluation of Pluripotent Cytokine TGF-β3 in Immunity

Reevaluation of Pluripotent Cytokine TGF-β3 in Immunity

  • Int J Mol Sci. 2018 Aug 1;19(8):2261. doi: 10.3390/ijms19082261.
Toshihiko Komai 1,  Tomohisa Okamura 2 3 4,  Mariko Inoue 5,  Kazuhiko Yamamoto 6 7 8,  Keishi Fujio 9
Affiliations

Affiliations

  • 1 Department of Allergy and Rheumatology, Graduate School of Medicine, The University of Tokyo, Tokyo 113-8655, Japan. tkomai-hok@umin.ac.jp.
  • 2 Department of Allergy and Rheumatology, Graduate School of Medicine, The University of Tokyo, Tokyo 113-8655, Japan. tomohisa-tky@umin.ac.jp.
  • 3 Department of Functional Genomics and Immunological Diseases, Graduate School of Medicine, The University of Tokyo, Tokyo 113-8655, Japan. tomohisa-tky@umin.ac.jp.
  • 4 Max Planck-The University of Tokyo Center for Integrative Inflammology, The University of Tokyo, Tokyo 153-8505, Japan. tomohisa-tky@umin.ac.jp.
  • 5 Department of Allergy and Rheumatology, Graduate School of Medicine, The University of Tokyo, Tokyo 113-8655, Japan. mariinoue-tky@umin.ac.jp.
  • 6 Department of Allergy and Rheumatology, Graduate School of Medicine, The University of Tokyo, Tokyo 113-8655, Japan. kazuhiko.yamamoto@riken.jp.
  • 7 Max Planck-The University of Tokyo Center for Integrative Inflammology, The University of Tokyo, Tokyo 153-8505, Japan. kazuhiko.yamamoto@riken.jp.
  • 8 Laboratory for Autoimmune Diseases, Center for Integrative Medical Sciences, RIKEN, Kanagawa 230-0045, Japan. kazuhiko.yamamoto@riken.jp.
  • 9 Department of Allergy and Rheumatology, Graduate School of Medicine, The University of Tokyo, Tokyo 113-8655, Japan. kfujio-tky@umin.ac.jp.
PMID: 30071700 DOI: 10.3390/ijms19082261
Abstract

Transforming growth factor (TGF)-βs are pluripotent cytokines with stimulatory and inhibitory properties for multiple types of immune cells. Analyses of genetic knockouts of each isoform of TGF-β have revealed differing expression patterns and distinct roles for the three mammalian isoforms of TGF-β. Considerable effort has been focused on understanding the molecular mechanisms of TGF-β1-mediated immune regulation, given its pivotal role in prohibiting systemic autoimmune disease. In recent years, functional similarities and differences between the TGF-β isoforms have delineated their distinct roles in the development of immunopathology and immune tolerance, with increased recent attention being focused on TGF-β3. In addition to the characteristic properties of each TGF-β 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-βs in immunity. Controlling TGF-β 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-β3 with comparisons to other TGF-β isoforms.

Keywords

autoimmune disease; fibrosis; immune tolerance; immunometabolism; regulatory T cell; transforming growth factor-β1; transforming growth factor-β3.

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