| Salt inducible kinase 1(SIK1)is a serine/threonine kinase that belongs to the SIK family,which currently has three members:SIK1,SIK2,and SIK3.The SIKs family controls gene expression by directly inhibiting the phosphorylation of transcription co-activators regulated by HDACâ…¡and CREB,thereby controlling the transcription program performed by these factors.SIK1 plays an important role in the metastasis of lung tumors,the transformation of chronic kidney disease into acute kidney injury,and gluconeogenesis in the body.It has been reported that SIK1 is closely related to the occurrence of inflammation.Previous experiments in our laboratory showed that SIK1 is highly expressed in germinal center B cells compared to naive B cells,which suggests that SIK1 may play an important role in lymphocyte development and function,especially in antibody immune response,but the specific role is still unclear.In order to explore the specific role of SIK1 gene in the development and function of lymphocytes,we used the CRISPR/Cas9 gene editing technology to construct Sik1 gene knockout mouse model,and used flow cytometry,ELISA,thymus-dependent immune response analysis and other methods to explore the role of Sik1 in lymphocyte development and function.The results shows that compared with wild-type mice,Sik1knockout mice have a decreased proportion of T1 B cells in the spleen and lymph nodes,an increase in the proportion of CD4~+T cells in the spleen,thymus,and lymph nodes,and an increase in serum Ig A levels.The ratio of germinal center cells and Ig G1 expression increased after sheep red blood cell stimulation.These phenotypes indicate that the Sik1gene may play an important role in the development of mouse B cells and T cells and immune response,especially the germinal center response.Sik1 is likely to play an inhibitory role in the occurrence of inflammation and the formation of germinal centers,which will provide an important experimental basis for the further study of the SIK1 gene function. |
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