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.
KeywordsArthritis Encephalomyelitis Bluestone
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.
- Castriconi R, Cantoni C, Della Chiesa M, Vitale M, Marcenaro E, Conte R, Biassoni R, Bottino C, Moretta L, Moretta A (2003) Transforming growth factor beta 1 inhibits expression of NKp30 and NKG2D receptors: consequences for the NK-mediated killing of dendritic cells. Proc Natl Acad Sci USA 100:4120–4125PubMedCrossRefGoogle Scholar
- Fadok VA, Bratton DL, Konowal A, Freed PW, Westcott JY, Henson PM (1998) Macrophages that have ingested apoptotic cells in vitro inhibit proinflammatory cytokine production through autocrine/paracrine mechanisms involving TGF-beta, PGE2, and PAF. J Clin Invest 101:890–898PubMedCrossRefGoogle Scholar
- Morelli AE, Zahorchak AF, Larregina AT, Colvin BL, Logar AJ, Takayama T, Falo LD, Thomson AW (2001) Cytokine production by mouse myeloid dendritic cells in relation to differentiation and terminal maturation induced by lipopolysaccharide or CD40 ligation. Blood 98:1512–1523PubMedCrossRefGoogle Scholar
- Strobl H, Bello-Fernandez C, Riedl E, Pickl WF, Majdic O, Lyman SD, Knapp W (1997) flt3 Ligand in cooperation with transforming growth factor-beta1 potentiates in vitro development of Langerhans-type dendritic cells and allows single-cell dendritic cell cluster formation under serum-free conditions. Blood 90:1425–1434PubMedGoogle Scholar