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Regulatory T cell Itch reins in Th2 inflammation

Cellular & Molecular Immunology volume 11, pages 126–128 (2014)Cite this article

Type 2 T helper (Th2) inflammation underlies common clinical disorders such as asthma, eczema and other atopic diseases. CD4+ regulatory T cells (Tregs) suppress over-exuberant immune responses in a variety of inflammatory microenvironments, including Th2 conditions. The transcription factor forkhead box protein 3 (Foxp3) controls Treg development, function and maintenance; however, mechanisms through which Tregs mitigate immune activation during different inflammatory situations remain largely unknown. In their recent article, Jin et al. report that Itch, an E3 ubiquitin ligase, is required to prevent Tregs from acquiring Th2-like phenotype and function.1 The authors created a novel Treg-specific Itch-deficient mouse (Itchfl/flFoxp3Cre) that enabled careful examination of Treg Itch in controlling Th2 inflammatory responses.

General Treg suppressive mechanisms involve contact-dependent inhibitory cell surface receptors (CTLA-4), competition for growth factors (CD25), hydrolysis of extracellular nucleotides (CD39, CD73) and induction of cell death (granzyme secretion).2 Additionally, Tregs suppress T cell skewing by acquiring specific T effector transcriptional programs that permit homing to a particular inflammatory microenvironment. Expression of the transcription factors T-bet, Irf4 and STAT3 regulate Treg suppressive activity in Th1, Th2 and Th17 inflammation, respectively (Table 1).3,4,5 Indeed, Treg-specific Irf4 knockout mice have dysregulated Th2 responses. However, we have limited data on the specific molecular pathways that Tregs employ to control Th2 inflammation.

Table 1 Role of selected proteins and the effect of their Treg-specific loss
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  1. Johns Hopkins University Division of Pulmonary and Critical Care Medicine, Baltimore, MD, USA

    Benjamin D Singer & Franco R D'Alessio

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  1. Benjamin D Singer
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  2. Franco R D'Alessio
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Correspondence to Franco R D'Alessio.

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Singer, B., D'Alessio, F. Regulatory T cell Itch reins in Th2 inflammation. Cell Mol Immunol 11, 126–128 (2014). https://doi.org/10.1038/cmi.2013.63

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