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Regulatory T cells use “Itch” to control asthma
WanJun Chen
WanJun Chen
Published October 25, 2013
Citation Information: J Clin Invest. 2013;123(11):4576-4578. https://doi.org/10.1172/JCI72477.
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Commentary

Regulatory T cells use “Itch” to control asthma

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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.

Authors

WanJun Chen

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Figure 1

Itch regulates Th2 cytokines in Tregs.

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Itch regulates Th2 cytokines in Tregs.
(A) In normal Tregs, Itch control...
(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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ISSN: 0021-9738 (print), 1558-8238 (online)

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