Abstract
Previously, we reported that B cell receptor associated protein 31 (BAP31) is a positive regulator on T-cells activation. Helper T cells [cluster of differentiation 4+ (CD4+) T cells] can regulate macrophage activation in adaptive immune response against pathogens. In this study, we elucidate that M1 and M2 macrophages polarization is significantly suppressed in Lck Cre-BAP31flox/flox mice or the co-culture system of CD4+ T cells from Lck Cre-BAP31flox/flox mice and macrophages from WT mice. It means that BAP31 may affect the regulation of CD4+ T cells on macrophages. Further studies suggest that BAP31 deficiency significantly reduce the expressions of T helper 1 (Th1)/ Th2/ Th17/ Th9/ Th22/ Treg cells-related cytokines and transcription factors. The inhibition of macrophages activation caused by BAP31 knockdown is due to the reduction of IFN-γ and IL-4 secreted by Th1 and Th2 cells. BAP31 also affects the levels of early activation markers (CD69 and CD25) of CD4+ T cells. Moreover, BAP31 deficiency downregulates the expression of TCRαβ-CD3 complex, and the adaptor proteins p-Zap70, p-Lck, and p-Lat in TCR signaling pathway. These results demonstrate that BAP31 deficiency inhibits TCR/CD3-mediated activation in CD4+ T cells and adversely affects macrophages polarization. These findings establish a theoretical foundation for the study of BAP31 in immunotherapy.
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The data used to support the findings of this study are available from the corresponding authors upon request.
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This research was supported by the Liaoning Revitalization Talents Program (XLYC1902063), Key Research and Development Plan of Liaoning Province (2020JH2/10300080), National Natural Science Foundation of China (31670770, 2016YFC1302402, 31370784), and Fundamental Research Funds for the Central Universities of China (N2120001).
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All authors contributed to the study conception and design. Experiments was designed by Bing Wang and Qing Yuan. Data collection and analysis were performed by Qing Yuan, Kun Wei Niu Bo Zhao and Li Jun Sun. The first draft of the manuscript was written by Qing Yuan. The manuscript was revised by Bing Wang and Xiao yu Wang. All authors read and approved the final manuscript.
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Yuan, Q., Niu, K., Sun, L. et al. BAP31 affects macrophage polarization through regulating helper T cells activation. J Mol Histol 53, 843–855 (2022). https://doi.org/10.1007/s10735-022-10095-5
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DOI: https://doi.org/10.1007/s10735-022-10095-5