The Th17 family: flexibility follows function

• Published in: Immunological reviews Vol. 252; no. 1; pp. 89 - 103
• Main Authors: Basu, Rajatava, Hatton, Robin D., Weaver, Casey T.
• Format: Journal Article
• Language: English
• Published: England Blackwell Publishing Ltd 01.03.2013
• Subjects: Cell Differentiation; cytokines; Differentiation; Forkhead Transcription Factors - genetics; Forkhead Transcription Factors - immunology; Gene Expression Regulation; Helper cells; Homeostasis; Homeostasis - immunology; Humans; Immune response; Immunoregulation; Interferon-gamma - genetics; Interferon-gamma - immunology; Interleukin-12 - genetics; Interleukin-12 - immunology; Interleukin-17 - genetics; Interleukin-17 - immunology; Lymphocytes T; Nuclear Receptor Subfamily 1, Group F, Member 3 - genetics; Nuclear Receptor Subfamily 1, Group F, Member 3 - immunology; plasticity; Plasticity (developmental); Signal Transduction; T-cell development; T-Lymphocytes, Regulatory - cytology; T-Lymphocytes, Regulatory - immunology; Th1 cells; Th1 Cells - cytology; Th1 Cells - immunology; Th17 cells; Th17 Cells - cytology; Th17 Cells - immunology; Th22 cells; Transforming Growth Factor beta - genetics; Transforming Growth Factor beta - immunology; Transforming growth factor- beta; Treg cells
• ISSN: 0105-2896; 1600-065X
• DOI: 10.1111/imr.12035

Summary Discovery of the T‐helper 17 (Th17) subset heralded a major shift in T‐cell biology and immune regulation. In addition to defining a new arm of the adaptive immune response, studies of the Th17 pathway have led to a greater appreciation of the developmental flexibility, or plasticity, that is a feature of T‐cell developmental programs. Since the initial finding that differentiation of Th17 cells is promoted by transforming growth factor‐β (TGFβ), it became clear that Th17 cell development overlapped that of induced regulatory T (iTreg) cells. Subsequent findings established that Th17 cells are also unusually flexible in their late developmental programming, demonstrating substantial overlap with conventional Th1 cells through mechanisms that are just beginning to be understood but would appear to have important implications for immunoregulation at homeostasis and in immune‐mediated diseases. Herein we examine the developmental and functional features of Th17 cells in relation to iTreg cells, Th1 cells, and Th22 cells, as a basis for understanding the contributions of this pathway to host defense, immune homeostasis, and immune‐mediated disease.