E3 ligase RNF128 restricts A. alternata-induced ILC2 activation and type 2 immune response in the murine lung

Abstract Allergic airway inflammation is a universal airway disease induced by inhaling allergens. Published data show that RNF128, an E3 ligase, promotes Th2 activation in the OVA-induced asthma model. Recent advances have shown that group 2 innate lymphoid cells (ILC2s) produce the cytokines IL-5...

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Main Authors: Chenghua Yan, Wendong Kuang, Guangqiang Ma, Feifei Guo, Liang Jin, Hongjiao Wan, Jinhua Zhu, Yongcui Liao, Haijun Tan, Liyuan Wang
Format: Article
Language:English
Published: Nature Portfolio 2025-01-01
Series:Scientific Reports
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Online Access:https://doi.org/10.1038/s41598-025-85227-4
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Summary:Abstract Allergic airway inflammation is a universal airway disease induced by inhaling allergens. Published data show that RNF128, an E3 ligase, promotes Th2 activation in the OVA-induced asthma model. Recent advances have shown that group 2 innate lymphoid cells (ILC2s) produce the cytokines IL-5 and IL-13 to mediate type 2 immune response. However, whether RNF128 regulates ILC2-dependent allergic lung inflammation remains unclear. In this study, we observed greater expression of the E3 ligase RNF128 in ILC2s than in other immune cells. RNF128 deficiency caused a selective increase in the number of peripheral mature ILC2s, and mice with RNF128 deficiency were more susceptible to Alternaria alternata (A. alternata) -induced allergic lung inflammation. Furthermore, RNF128 deficiency increased recruitment of eosinophils and levels of IL-5 and IL-13 in the bronchoalveolar lavage fluid. RNF128 effectively inhibited the expansion of ILC2s and the number of IL-5- and IL-13-producing ILC2s. Specially, RNF128 deficiency promoted the expression of the interleukin-33 (IL-33) receptor ST2 in A. alternata-induced allergic lung inflammation. Above all, our study demonstrated that RNF128 played a key role in A. alternata-induced ILC2 activation and type 2 immune response, suggesting that RNF128 may be an effective therapeutic target for allergic lung inflammation initiated by ILC2s.
ISSN:2045-2322