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Review
. 2010 Jun;147(6):781-92.
doi: 10.1093/jb/mvq043. Epub 2010 Apr 20.

Cellular and molecular basis for the regulation of inflammation by TGF-beta

Akihiko Yoshimura  1 , Yu Wakabayashi, Tomoaki Mori
Affiliations
Review

VSports最新版本 - Cellular and molecular basis for the regulation of inflammation by TGF-beta

"V体育安卓版" Akihiko Yoshimura et al. J Biochem. 2010 Jun.

Abstract

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 VSports手机版. 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. .

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Figures

Fig. 1
Fig. 1
Schematic overview of Th cell differentiation. See detail in the text.
Fig. 2
Fig. 2
Effect of TGF-β on immune cells. TGF-β inhibits proliferation of various immune cells, inhibits Th1 and Th2 differentiation, induces Th17 and iTregs and inhibits maturation of other cells such as CD8+ CTL, NK cell, DC and macrophages.
Fig. 3
Fig. 3
Role of TGF-β in Th17 and iTreg differentiation. (A) RORγt, a master transcription factor for Th17 is induced by TGF-β+ IL-6, which requires STAT3 but not Smad2/3/4. Smad-independent mechanism is shown as ‘?'. Foxp3, a master transcription factor for Treg is induced by TGF-β, and Foxp3 levels become higher by the IL-2/STAT5 signaling. This step is Smad2/3 dependent. STAT3 and STAT5 inhibit Foxp3 and RORγt induction, respectively. (B) Regulation of iTreg and Th17 by IL-6. In iTreg condition, Foxp3 binds to RORγt, thereby suppressing transcriptional activity of RORγt and Th17 differentiation. STAT3 induces IRF4 and c-Maf, which supports expression of RORγt expression. STAT3 also inhibits Foxp3 expression. Suppression of IL-2, IFN-γ and IL-4 by TGF-β, which is Smad2/3-dependent also promotes Th17 differentiation.
Fig. 4
Fig. 4
Reciprocal inhibition mechanism by TGF-β and IFN-γ. IFN-γ receptor activates STAT1, then STAT1-target genes such as Smad7 and unidentified molecules inhibit TGF-β signaling. TGF-β and Smads also inhibits the IFN-γ/STAT1 pathway by several ways. See detail in the text.
See this image and copyright information in PMC

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