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J Exp Med. 2018 Nov 5;215(11):2850-2867. doi: 10.1084/jem.20172026. Epub 2018 Sep 17.

USP38 critically promotes asthmatic pathogenesis by stabilizing JunB protein.

Author information

1
Chinese Academy of Sciences (CAS) Key Laboratory of Tissue Microenvironment and Tumor, CAS Center for Excellence in Molecular Cell Science, Shanghai Institute of Nutrition and Health, Shanghai Institutes for Biological Sciences, University of Chinese Academy of Sciences, Chinese Academy of Sciences, Shanghai, China.
2
School of Life Science and Technology, ShanghaiTech University, Shanghai, China.
3
Chinese Academy of Sciences (CAS) Key Laboratory of Tissue Microenvironment and Tumor, CAS Center for Excellence in Molecular Cell Science, Shanghai Institute of Nutrition and Health, Shanghai Institutes for Biological Sciences, University of Chinese Academy of Sciences, Chinese Academy of Sciences, Shanghai, China ycqian@sibs.ac.cn.

Abstract

Th2 immune response is critical for allergic asthma pathogenesis. Molecular mechanisms for regulating Th2 immunity are still not well understood. Here we report that the ubiquitin-specific protease USP38 is crucial for Th2-mediated allergic asthma. TCR stimulation up-regulated the USP38 level, and USP38 in turn mediated the protein stabilization of JunB, a transcription factor specific for Th2 development. Consequently, USP38 was specifically required for TCR-induced production of Th2 cytokines and Th2 development both in vitro and in vivo, and USP38-deficient mice were resistant to asthma pathogenesis induced by OVA or HDM. Mechanistically, USP38 directly associated with JunB, deubiquitinated Lys-48-linked poly-ubiquitination of JunB, and consequently blocked TCR-induced JunB turnover. USP38 represents the first identified deubiquitinase specifically for Th2 immunity and the associated asthma.

PMID:
30224386
PMCID:
PMC6219735
[Available on 2019-05-05]
DOI:
10.1084/jem.20172026

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