Beijing Institute of Brain Disorders, Laboratory of Brain Disorders, Ministry of Science and Technology, Collaborative Innovation Center for Brain Disorders, Capital Medical University, Beijing, China.
Department of Neurology, Beijing Chaoyang Hospital, Capital Medical University, Beijing, China.
Immunology. 2021 Sep;164(1):190-206. doi: 10.1111/imm.13365. Epub 2021 Jun 2.
It is important to characterize novel proteins involved in T- and B-cell responses. Our previous study demonstrated that a novel protein, Mus musculus Gm40600, reduced the proliferation of Mus musculus plasmablast (PB)-like SP 2/0 cells and B-cell responses induced in vitro by LPS. In the present study, we revealed that Gm40600 directly promoted CD4 T-cell responses to indirectly up-regulate B-cell responses. Importantly, we found that CD4 T-cell responses, including T-cell activation and differentiation and cytokine production, were increased in Gm40600 transgenic (Tg) mice and were reduced in Gm40600 knockout (KO) mice. Finally, we demonstrated that Gm40600 promoted the Ahnak-mediated calcium signalling pathway by interacting with Ahnak to maintain a cytoplasmic lateral location of Ahnak in CD4 T cells. Collectively, our data suggest that Gm40600 promotes CD4 T-cell activation to up-regulate the B-cell response via interacting with Ahnak to promote the calcium signalling pathway. The results suggest that targeting Gm40600 may be a means to control CD4 T-cell-related diseases.
研究新型蛋白在 T 细胞和 B 细胞反应中的作用具有重要意义。我们之前的研究表明，一种新型蛋白 Mus musculus Gm40600 可降低 Mus musculus 类浆细胞（PB）样 SP2/0 细胞的增殖和 LPS 体外诱导的 B 细胞反应。本研究揭示 Gm40600 可直接促进 CD4 T 细胞反应，从而间接上调 B 细胞反应。重要的是，我们发现 Gm40600 转基因（Tg）小鼠的 CD4 T 细胞反应（包括 T 细胞激活、分化和细胞因子产生）增加，而 Gm40600 敲除（KO）小鼠的 CD4 T 细胞反应减少。最后，我们证明 Gm40600 通过与 Ahnak 相互作用促进 Ahnak 介导的钙信号通路，从而维持 CD4 T 细胞中 Ahnak 的细胞质侧位。总之，我们的数据表明，Gm40600 通过与 Ahnak 相互作用促进钙信号通路，从而促进 CD4 T 细胞的激活，上调 B 细胞反应。这些结果提示靶向 Gm40600 可能是控制与 CD4 T 细胞相关疾病的一种手段。
