期刊
AUTOPHAGY
卷 14, 期 3, 页码 450-464出版社
TAYLOR & FRANCIS INC
DOI: 10.1080/15548627.2017.1421884
关键词
Antigen presentation; asthma; autophagy; B cell; IL4
类别
资金
- National Natural Science Foundation of China [81522019, 31270966, 81471567]
- National Key Basic Research Program of China [2013CB530502]
- National Key Research and Development Program of China [2016YFA0501801]
- Public Welfare Technology Application Research Project of Zhejiang Province [2013C33155]
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.
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