AUTHOR=Wu Guo-Rao , Zhou Min , Wang Yi , Zhou Qing , Zhang Lei , He Long , Zhang Shu , Yu Qilin , Xu Yongjian , Zhao Jianping , Xiong Weining , Wang Cong-Yi 

TITLE=Blockade of Mbd2 by siRNA-loaded liposomes protects mice against OVA-induced allergic airway inflammation via repressing M2 macrophage production

JOURNAL=Frontiers in Immunology

VOLUME=13

YEAR=2022

URL=https://www.frontiersin.org/journals/immunology/articles/10.3389/fimmu.2022.930103

DOI=10.3389/fimmu.2022.930103

ISSN=1664-3224

ABSTRACT=<sec><title>Objective</title><p>To address the role of methyl-CpG-binding domain 2 (MBD2) in the pathogenesis of asthma and its potential as a target for the asthmatic therapy.</p></sec><sec><title>Methods</title><p>Studies were conducted in asthmatic patients and macrophage-specific <italic>Mbd2</italic> knockout mice to dissect the role of MBD2 in asthma pathogenesis. Additionally, RNAi-based therapy with <italic>Mbd2</italic> siRNA-loaded liposomes was conducted in an ovalbumin (OVA)-induced allergic airway inflammation mouse model.</p></sec><sec><title>Results</title><p>Asthmatic patients and mice challenged with OVA exhibited upregulated MBD2 expression in macrophages, especially in alternatively activated (M2) macrophages. In particular, macrophage-specific knockout of <italic>Mbd2</italic> protected mice from OVA-induced allergic airway inflammation and suppressed the M2 program. Notably, intratracheal administration of liposomes carrying <italic>Mbd2</italic> siRNA decreased the expression of Mbd2 and prevented OVA-induced allergic airway inflammation in mice, as indicated by the attenuated airway inflammation and mucus production.</p></sec><sec><title>Conclusions</title><p>The above data indicate that Mbd2 implicates in the pathogenesis of asthma predominantly by regulating the polarization of M2 macrophages, which supports that Mbd2 could be a viable target for treatment of asthma in clinical settings.</p></sec>