Nuclear receptor corepressor 1 deficiency exacerbates asthma by modulating macrophage polarization

Chenchen Hou; Lifeng Yan; Ke Sun; Tianyu Zhou; Yuxin Zou; Weining Xiong; Sheng-Zhong Duan

doi:10.1038/s41420-023-01724-3

Nuclear receptor corepressor 1 deficiency exacerbates asthma by modulating macrophage polarization

Cell Death Discov. 2023 Nov 29;9(1):429. doi: 10.1038/s41420-023-01724-3.

Authors

Chenchen Hou^#¹, Lifeng Yan^#¹, Ke Sun^#², Tianyu Zhou^{1

3}, Yuxin Zou¹, Weining Xiong^{4

5}, Sheng-Zhong Duan^{6

7}

Affiliations

¹ Department of Respiratory and Critical Care Medicine, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, 200011, China.
² Division of Nephrology, Huashan Hospital, Fudan University, Shanghai, 200031, China.
³ Shanghai Key Laboratory of Tissue Engineering, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, 200011, China.
⁴ Department of Respiratory and Critical Care Medicine, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, 200011, China. xiongdoctor@qq.com.
⁵ Shanghai Key Laboratory of Tissue Engineering, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, 200011, China. xiongdoctor@qq.com.
⁶ Laboratory of Oral Microbiota and Systemic Diseases, Shanghai Ninth People's Hospital, College of Stomatology, Shanghai Jiao Tong University School of Medicine, Shanghai, 200011, China. duansz2008@hotmail.com.
⁷ National Center for Stomatology, National Clinical Research Center for Oral Diseases, Shanghai Key Laboratory of Stomatology, Shanghai, 200011, China. duansz2008@hotmail.com.

^# Contributed equally.

Abstract

Macrophage polarization plays an important role in asthma. Nuclear receptor corepressor 1 (NCOR1) plays an important role in metabolic and cardiovascular diseases by regulating the function of macrophages. The aim of this research was to examine the role and mechanism of macrophage NCOR1 in the development of asthma. We used ovalbumin (OVA) to induce macrophage NCOR1-deficient mice for asthma formation. Our results revealed that macrophage NCOR1 deficiency markedly enhanced allergic airway inflammation. In addition, NCOR1 deficiency in macrophages was found to enhance M2 polarization. Mechanistic studies suggested that NCOR1 promoted macrophage polarization by interacting with PPARγ, contributing to the pathogenesis of asthma. In conclusion, macrophage NCOR1 deficiency promoted the regulation of M2 programming by enhancing PPARγ expression to exacerbate asthma. Macrophage NCOR1 might be a potential target for the treatment of asthma.