Gm40600 promotes CD4⁺ T-cell responses by interacting with Ahnak

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.