BCR-Associated Protein 31 Regulates Macrophages Polarization and Wound Healing Function via Early Growth Response 2/C/EBPβ and IL-4Rα/C/EBPβ Pathways

Author:

Yuan Qing1ORCID,Zhao Bo1,Cao Yu-hua1,Yan Jia-cheng1,Sun Li-jun1,Liu Xia1,Xu Yang1,Wang Xiao-yu1ORCID,Wang Bing1ORCID

Affiliation:

1. College of Life Science and Health, Northeastern University, Hunnan Xinqu, Shenyang, Liaoning, China

Abstract

Abstract The BCR-associated protein 31 (BAP31), a transmembrane protein in the endoplasmic reticulum, participates in the regulation of immune cells, such as microglia and T cells, and has potential functions in macrophages that remain to be unexplored. In this study, we designed and bred macrophage-specific BAP31 knockdown mice to detect the polarization and functions of macrophages. The results revealed that M2 macrophage-associated genes were suppressed in mouse bone marrow–derived macrophages of Lyz2 Cre-BAP31flox/flox mice. Multiple macrophage-associated transcription factors were demonstrated to be able to be regulated by BAP31. Among these factors, C/EBPβ was the most significantly decreased and was regulated by early growth response 2. BAP31 could also affect C/EBPβ via modulating IL-4Rα ubiquitination and proteasome degradation in IL-4–stimulated macrophages. Furthermore, we found that BAP31 affects macrophages functions, including angiogenesis and skin fibrosis, during the wound healing process through IL-4Rα, as confirmed by infection with adeno-associated virus–short hairpin (sh)-IL-4Rα in Lyz2 Cre-BAP31flox/flox mice. Our findings indicate a novel mechanism of BAP31 in regulating macrophages and provide potential solutions for the prevention and treatment of chronic wounds.

Funder

Liaoning Revitalization Talents Program

Key Research and development plan of Liaoning province

National Natural Science Foundation of China

MOE | Fundamental Research Funds for the Central Universities

Publisher

The American Association of Immunologists

Subject

Immunology,Immunology and Allergy

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