Butyrophilin 2A2 promotes T cell immunoregulation via CD45 phosphatase activation and protects against murine autoimmune glomerulonephritis and pregnancy loss.

ABSTRACT: B7 costimulatory family member Butyrophilin 2A2 (BTN2A2) is predominantly expressed by antigen presenting cells and regulates T cell immunity, but molecular mechanisms are unclear. Using immunoblots analyzing TCR-initiated signaling intermediaries, co-immunoprecipitation studies, confocal microscopy, structural modeling-guided mutational analyses, and microscale thermophoresis, we demonstrate that BTN2A2 directly interacts with CD45RO, resulting in CD45 retention within the immune synapse during TCR activation. Recombinant BTN2A2 increases murine CD4+Foxp3+ regulatory T cells (Treg) and reduces T helper 17 (Th17) cells in vitro through mechanisms dependent on CD45 phosphatase activity. BTN2A2 therapy alleviates disease severity in murine nephrotoxic glomerulonephritis and autoimmune miscar

SUBMITTER: Ali S 

PROVIDER: S-EPMC12873404 | biostudies-literature | 2026 Jan

REPOSITORIES: biostudies-literature