Role of TGF-β in Immune Suppression and Inflammation
Transforming growth factor-β (TGF-β) a family of cytokines ubiquitously produced and responded to by almost all cells, plays critical roles in the regulation of immune responses in the physiological as well as pathological settings. While traditionally considered an immunologically “non-specific” regulatory cytokine influencing the phenotype and function of innate and adaptive immune cells, TGF-β has been recently uncovered to “specifically” reprogram naïve CD4+ T cells to certain T cell lineages. In this regard, TGF-β is found to serve as a “master switch” in programming naïve CD4+ T lymphocytes into either Foxp3+ regulatory T cells (Treg cells) or Th17 pro-inflammatory effector cells in the context of T cell receptor engagement and respective cytokine milieu. With continuous expansion of our knowledge of TGF-β regulation of immune responses, it is imperative to understand the common and individual molecular mechanisms by which TGF-β signals in immune cells. It is also important to explore the pathways to apply the basic concept to the development of immunotherapy in experimental, and ultimately clinical, settings. In this chapter, we will highlight key findings on how TGF-β influences the innate and adaptive immune systems, with focus on recent progress concerning TGF-β regulation of T cell differentiation/function, and discuss the link between TGF-β regulation of immune responses and pathogenesis of autoimmunity, chronic inflammation and cancer.
KeywordsNatural Killer Cell Th17 Cell Experimental Autoimmune Encephalomyelitis Treg Cell iNKT Cell
We thank Drs. T. Maruyama and P. Zhang, MIS, NIDCR, NIH for critically reading the manuscript. This research was supported by the intramural Research program of the NIH, National Institute for Dental and Craniofacial Research.
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