Regulatory T cells use "Itch" to control asthma - PubMed (original) (raw)

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. 2013 Nov;123(11):4576-8.

doi: 10.1172/JCI72477. Epub 2013 Oct 25.

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Regulatory T cells use "Itch" to control asthma

WanJun Chen. J Clin Invest. 2013 Nov.

Abstract

Regulatory T cells (Tregs) control type 2 T helper cell-mediated (Th2-mediated) lung inflammation, but the molecular mechanisms by which Tregs execute this activity remain elusive. In this issue of the JCI, Jin et al. reveal that Itch, a HECT-type E3 ubiquitin ligase in Tregs, plays a specific role in restraining Th2 cell responses. This finding has important implications for understanding the pathogenesis of allergy and asthma.

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Figure 1

Figure 1. Itch regulates Th2 cytokines in Tregs.

(A) In normal Tregs, Itch controls the expression of GATA3 and phosphorylation of STAT6, which prevents Il4 gene transcription and IL-4 production. Thus, no Th2 cytokines (IL-4, IL-5, and IL-13) are produced or secreted by Itch-sufficient normal T cells; (B) In the absence of Itch, as evident in Itchf/fFoxp3Cre mice, Tregs cannot control GATA3 and STAT6, which results in increased GATA3 expression and STAT6 activation. Consequently, Il4 transcription is activated and IL-4 production is increased. IL-4 secreted by Itch-deficient Tregs instructs the normal naive CD4+ T cells to initiate a Th2 cell differentiation program for the secretion of large amounts of IL-4, IL-5, and IL-13, which together lead to uncontrolled Th2-type inflammation, especially in the lungs of Itchf/fFoxp3Cre mice. Red “X” indicates a block or deletion of the target molecules; black arrows indicate positive effects, and red lines indicate negative effects. Dotted line indicates no available evidence yet.

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References

    1. Littman DR, Rudensky AY. Th17 and regulatory T cells in mediating and restraining inflammation. Cell. 2010;140(6):845–858. doi: 10.1016/j.cell.2010.02.021. - DOI - PubMed
    1. Ohkura N, Kitagawa Y, Sakaguchi S. Development and maintenance of regulatory T cells. Immunity. 2013;38(3):414–423. doi: 10.1016/j.immuni.2013.03.002. - DOI - PubMed
    1. Chen W, Wahl SM. TGF-β: the missing link in CD4+CD25+ regulatory T cell-mediated immunosuppression. Cytokine Growth Factor Rev. 2003;14(2):85–89. doi: 10.1016/S1359-6101(03)00003-0. - DOI - PubMed
    1. Shevach EM. Mechanisms of foxp3+ T regulatory cell-mediated suppression. . Immunity. 2009;30(5):636–645. doi: 10.1016/j.immuni.2009.04.010. - DOI - PubMed
    1. Chaudhry A, Rudensky AY. Control of inflammation by integration of environmental cues by regulatory T cells. J Clin Invest. 2013;123(3):939–944. doi: 10.1172/JCI57175. - DOI - PMC - PubMed

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