Cellular and molecular basis for the regulation of inflammation by TGF-beta.
Transforming growth factor-beta (TGF-beta) has been shown to play an essential role in the suppression of inflammation, yet recent studies have revealed the positive roles of TGF-beta in inflammatory responses. For example, TGF-beta induces Foxp3-positive regulatory T cells (iTregs) in the presence of interleukin-2 (IL-2), while in the presence of IL-6, it induces pathogenic IL-17 producing Th17 cells. TGF-beta inhibits the proliferation of immune cells as well as cytokine production via Foxp3-dependent and -independent mechanisms. Little is known about molecular mechanisms involved in immune suppression via TGF-beta; however, Smad2/3 have been shown to play essential roles in Foxp3 induction as well as in IL-2 and IFN-gamma suppression, whereas Th17 differentiation is promoted via the Smad-independent pathway. Interaction between TGF-beta and other cytokine signaling is important in establishing the balance of immunity and tolerance.
Yoshimura
Akihiko
A
Department of Microbiology and Immunology, Keio University School of Medicine, 35 Shinanomachi, Shinjuku-ku, Tokyo 160-8582, Japan. yoshimura@a6.keio.jp
Wakabayashi
Yu
Y
Mori
Tomoaki
T
D000818:Animals; D002454:Cell Differentiation / Q000502:physiology; D007249:Inflammation / Q000276:immunology* / Q000503:physiopathology; D051379:Mice; D015398:Signal Transduction / Q000276:immunology; D051896:Smad Proteins, Receptor-Regulated / Q000502:physiology*; D016176:T-Lymphocyte Subsets / Q000502:physiology; D050378:T-Lymphocytes, Regulatory / Q000502:physiology; D016212:Transforming Growth Factor beta / Q000276:immunology* / Q000378:metabolism / Q000494:pharmacology*
D051896:Smad Proteins, Receptor-Regulated; D016212:Transforming Growth Factor beta
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