Targeting epithelial cell-derived TWIST1 alleviates allergic asthma.

It is well known that the T Helper (Th)2 bias plays a critical role in allergic asthma. Whereas the Th2 bias is maintained in the local tissues is uncertain. IL-33 is vital for the development of the Th2 polarization. TWIST-1 has an effect on regulating cellular functions. The aberrant activation of RAS sustains certain cellular activities. The aim of this study is to study the role of the interaction between activation of TWIST1 and RAS in inducing and maintaining Th2 polarization in allergic asthma. The epithelial cells of the airways (AEC) were isolated from the broncho-alveolar lavage fluids in patients with asthma. The mediators involved in the over-expression of IL-33 were determined by RNA sequencing. A mouse model was established to test the role of TWIST1 and RAS in developing allergic asthma. We observed a strong expression of TWIST1 in patients with allergic asthma that showed a positive correlation with asthmatic responses. TWIST1 favored the expression of the IL-33 in the AEC. Twist1-deficient AEC-carrying mice did not induce Th2 polarization in the airways. The expression TWIST1 in AECs was positively associated with RAS activation in AECs in patients with allergic asthma. The interaction between RAS and TWIST1 in AECs sustained airway allergic inflammation. Inhibition of TWIST1 or RAS prevented asthma-like inflammation in the mouse airways. In summary, the interaction between TWIST1 and RAS induces and maintains IL-33 expression in AECs to facilitate allergic inflammation in the respiratory tract. Inhibition of TWIST1 or RAS can prevent experimental allergic asthma. Copyright © 2022. Published by Elsevier Inc.

Citation

Huanping Zhang, Yanfen Wang, Xiaoxue Chen, Aizhi Zhang, Lijun Hou, Jingyi Hong, Jiangqi Liu, Zhiqiang Liu, Pingchang Yang. Targeting epithelial cell-derived TWIST1 alleviates allergic asthma. Cellular signalling. 2023 Feb;102:110552

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PMID: 36481410

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