BET proteins inhibitor JQ1 impairs GM-CSF-promoted peritoneal macrophage self-renewal and IL-4-induced alternative polarization

Chen，Xue1; Jiang，Qiong2; Ren，Laibin3; Ren，Hongyu3; Xu，Haizhao6; Wang，Jinyong2; Wang，Pengbo7; Chen，Shanze2,3; Hua，Yuanqi3; Ren，Sichong4; Huang，Ning3; Zhang，Lanlan5; Xiao，Lijia1

2023-11-01

10.1016/j.intimp.2023.110942

International Immunopharmacology   Impact Factor & Quartile

1567-5769

1878-1705

Peritoneal macrophages (PMs), which resided in peritoneal cavity, are crucial to maintain tissue homeostasis and immunity. Macrophage self-renewal and polarization states are critical for PM population homeostasis and function. However, the underlying molecular mechanism that regulates self-renewal and polarization of PMs is still unclear and needs to be explored. Here, we demonstrated that PMs self-renewal was stimulated by granulocyte macrophage colony-stimulating factor (GM-CSF), but not by macrophage colony-stimulating factor (M−CSF). Pharmacological inhibition of Bromodomain & Extraterminal (BET) Proteins by either JQ1 or ARV-825 significantly reduced GM-CSF-dependent peritoneal macrophage self-renewal by abrogating cell proliferation and decreasing self-renewal-related gene expression, such as MYC and Klf4, at transcriptional and protein levels. In addition, transcriptomic analysis showed that JQ1 blocked alternative PMs polarization by downregulating key transcriptional factor IRF4 expression, but not the activation of AKT or STAT6 in PMs. These findings illustrated that the significance of BET family proteins in GM-CSF-induced PMs self-renewal and IL-4-induced alternative polarization.

Alternative PMs polarization BET Proteins JQ1 Peritoneal macrophages Self-renewal

SCI

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Natural Science Foundation of Guangdong Province[2019A1515012079];Key Science and Technology Program of Shaanxi Province[2019YFS0230];Natural Science Foundation of Guangdong Province[2021A1515010478];Guangdong Provincial Key Laboratory of Urology[2022A1515011966];Natural Science Foundation of Guangdong Province[2214050008970];National Natural Science Foundation of China[32100734];National Natural Science Foundation of China[32100914];National Natural Science Foundation of China[81803183];National Natural Science Foundation of China[81974457];

Immunology ; Pharmacology & Pharmacy

Immunology ; Pharmacology & Pharmacy

WOS:001078660000001

ELSEVIER

PHARMACOLOGY & TOXICOLOGY

2-s2.0-85171165389

Scopus

1.Department of Clinical Laboratory Medicine Center,Shenzhen Hospital,Southern Medical University,Shenzhen,Guangdong,518101,China
2.Shenzhen Institute of Respiratory Disease,Shenzhen People's Hospital (The Second Clinical Medical College,Jinan University,The First Affiliated Hospital,Southern University of Science and Technology),Shenzhen,Guangdong,518107,China
3.Department of Pathophysiology,West China College of Preclinical and Forensic Medicine,Sichuan University,Chengdu,Sichuan,610041,China
4.Department of Nephrology,the First Affiliated Hospital of Chengdu Medical College,Chengdu,Sichuan,610500,China
5.Division of Pulmonary Diseases,State Key Laboratory of Biotherapy,West China Hospital of Sichuan University,Chengdu,Sichuan,610041,China
6.Department of Respiratory,The First Affiliated Hospital,School of Medicine,Southern University of Science and Technology,Guangdong,518055,China
7.School of Professional Studies,Columbia University,NY,10027,United States

Chen，Xue,Jiang，Qiong,Ren，Laibin,et al. BET proteins inhibitor JQ1 impairs GM-CSF-promoted peritoneal macrophage self-renewal and IL-4-induced alternative polarization[J]. International Immunopharmacology,2023,124.

Chen，Xue.,Jiang，Qiong.,Ren，Laibin.,Ren，Hongyu.,Xu，Haizhao.,...&Xiao，Lijia.(2023).BET proteins inhibitor JQ1 impairs GM-CSF-promoted peritoneal macrophage self-renewal and IL-4-induced alternative polarization.International Immunopharmacology,124.

Chen，Xue,et al."BET proteins inhibitor JQ1 impairs GM-CSF-promoted peritoneal macrophage self-renewal and IL-4-induced alternative polarization".International Immunopharmacology 124(2023).