1. Academic Validation
  2. IL4 (interleukin 4) induces autophagy in B cells leading to exacerbated asthma

IL4 (interleukin 4) induces autophagy in B cells leading to exacerbated asthma

  • Autophagy. 2018;14(3):450-464. doi: 10.1080/15548627.2017.1421884.
Fucan Xia 1 Changwen Deng 2 Yanyan Jiang 3 Yulan Qu 2 Jiewen Deng 3 Zhijian Cai 1 Yuanyuan Ding 4 Zhenhong Guo 3 Jianli Wang 1
Affiliations

Affiliations

  • 1 a Institute of Immunology , Zhejiang University School of Medicine , Hangzhou , China.
  • 2 b Department of Respiratory Medicine , Changhai Hospital , Second Military Medical University , Shanghai , China.
  • 3 c National Key Laboratory of Medical Immunology & Institute of Immunology , Second Military Medical University , Shanghai , China.
  • 4 d National Key Laboratory of Medical Molecular Biology & Department of Immunology , Institute of Basic Medical Sciences , Peking Union Medical College , Chinese Academy of Medical Sciences , Beijing , China.
Abstract

Allergic asthma is a common airway inflammatory disease in which B cells play important roles through IgE production and antigen presentation. SNP (single nucleotide polymorphism) analysis showed that Atg (autophagy-related) allele mutations are involved in asthma. It has been demonstrated that macroautophagy/Autophagy is essential for B cell survival, plasma cell differentiation and immunological memory maintenance. However, whether B cell Autophagy participates in asthma pathogenesis remains to be investigated. In this report, we found that Autophagy was enhanced in pulmonary B cells from asthma-prone mice. Autophagy deficiency in B cells led to attenuated immunopathological symptoms in asthma-prone mice. Further investigation showed that IL4 (interleukin 4), a key effector Th2 cytokine in allergic asthma, was critical for Autophagy induction in B cells both in vivo and in vitro, which further sustained B cell survival and enhanced antigen presentation by B cells. Moreover, IL4-induced Autophagy depended on JAK signaling via an MTOR-independent, PtdIns3K-dependent pathway. Together, our data indicate that B cell Autophagy aggravates experimental asthma through multiple mechanisms.

Keywords

Antigen presentation; B cell; IL4; asthma; autophagy.

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