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-BAP31^flox/flox mice or the co-culture system of CD4⁺ T cells from Lck Cre-BAP31^flox/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.

以前，我们报道了 B 细胞受体相关蛋白 31 (BAP31) 是 T 细胞活化的正调节剂。辅助 T 细胞 [分化簇 4 ⁺ (CD4 ⁺ ) T 细胞] 可以在针对病原体的适应性免疫反应中调节巨噬细胞活化。在这项研究中，我们阐明了在 Lck Cre-BAP31 ^{flox/flox小鼠或来自 Lck Cre-BAP31 flox/flox小鼠的 CD4 +} T 细胞和来自 WT 小鼠的巨噬细胞的共培养系统中，M1 和 M2 巨噬细胞极化受到显着抑制。这意味着BAP31可能影响CD4 ^+的调节巨噬细胞上的 T 细胞。进一步的研究表明，BAP31 缺乏会显着降低 T 辅助细胞 1 (Th1)/ Th2/ Th17/ Th9/ Th22/ Treg 细胞相关细胞因子和转录因子的表达。BAP31 敲低引起的巨噬细胞活化抑制是由于 Th1 和 Th2 细胞分泌的 IFN-γ 和 IL-4 的减少。BAP31 还影响 CD4 ⁺ T 细胞的早期激活标志物（CD69 和 CD25）的水平。此外，BAP31 缺乏会下调 TCRαβ-CD3 复合物以及 TCR 信号通路中衔接蛋白 p-Zap70、p-Lck 和 p-Lat 的表达。这些结果表明 BAP31 缺乏抑制 TCR/CD3 介导的 CD4 ⁺T 细胞并对巨噬细胞极化产生不利影响。这些发现为BAP31在免疫治疗中的研究奠定了理论基础。