Journal
JOURNAL OF IMMUNOLOGY
Volume 209, Issue 6, Pages 1059-1070Publisher
AMER ASSOC IMMUNOLOGISTS
DOI: 10.4049/jimmunol.2200044
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Funding
- Liaoning Revitalization Talents Program [XLYC1902063]
- Key Research and Development Plan of Liaoning Province [2020JH2/10300080]
- National Natural Science Foundation of China [31670770, 2016YFC1302402, 31370784]
- Fundamental Research Funds for the Central Universities of China [N2120001]
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This study reveals a novel mechanism of BAP31 in regulating macrophages and provides potential solutions for the prevention and treatment of chronic wounds.
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-BAP31(flox/flox) mice. Multiple macrophage-associated transcription factors were demonstrated to be able to be regulated by BAP31. Among these factors, C/EBPb was the most significantly decreased and was regulated by early growth response 2. BAP31 could also affect C/EBP beta via modulating IL-4R alpha 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-4R alpha, as confirmed by infection with adeno-associated virus-short hairpin (sh)-IL-4R alpha in Lyz2 Cre-BAP31(flox/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.
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