Journal
IMMUNOLOGY
Volume 164, Issue 1, Pages 190-206Publisher
WILEY
DOI: 10.1111/imm.13365
Keywords
Gm40600; B cells; CD4(+) T cells; Th cells; Ahnak
Categories
Funding
- National Natural Science Foundation of China [82071758, 31770956, 81704151]
- Natural Science Foundation of Beijing Municipality [7182121]
- Beijing Municipal Commission of Education [KM201710025014]
- China Postdoctoral Science Foundation-Funded Project [2019M664000]
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The novel protein Gm40600 directly promotes CD4(+) T-cell responses to indirectly up-regulate B-cell responses. By interacting with Ahnak, Gm40600 is shown to promote CD4(+) T-cell activation, suggesting it may be a potential target to control CD4(+) T-cell-related diseases.
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.
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