A dominant function of LynB kinase in preventing autoimmunity.

ABSTRACT: Here, we report that the LynB splice variant of the Src-family kinase Lyn exerts a dominant immunosuppressive function in vivo, whereas the LynA isoform is uniquely required to restrain autoimmunity in female mice. We used CRISPR-Cas9 gene editing to constrain lyn splicing and expression, generating single-isoform LynA knockout (LynA^KO) or LynB^KO mice. Autoimmune disease in total Lyn^KO mice is characterized by production of antinuclear antibodies, glomerulonephritis, impaired B cell development, and overabundance of activated B cells and proinflammatory myeloid cells. Expression of LynA or LynB alone uncoupled the developmental phenotype from the autoimmune disease: B cell transitional populations were restored, but myeloid cells and differentiated B

SUBMITTER: Brian BF 

PROVIDER: S-EPMC9032976 | biostudies-literature | 2022 Apr

REPOSITORIES: biostudies-literature