Connexin-43: More than just a gap junction protein. Connexin-43 controls CD4+ T cell activation and clonal expansion

Abstract Activation and proliferation of antigen specific T cells depends on the interaction multiple signaling molecules with TCR/CD3 complex. We report that expression connexin 43 (Cx43), a gap junction protein, is critical for expansion antigen-specific or self-reactive effector CD4 +T cells. While mediated intercellular communication has been main focus research, cytoplasmic C-terminus Cx43 functions independent membrane channel forming properties may act as docking molecule assembling complexes including immunological synapse. also Cx43-deficient transferred into recipient mice immunized cognate antigenic peptide adjuvant expanded poorly compared to wild type This protected from experimental autoimmune encephalomyelitis (EAE). Decreased protects lymphopenic repopulated naive, deficient cells, inflammatory bowel disease. have found defect affecting Erk, p38 Akt pathways. Transcriptome RNA-seq analysis comparing gene profiles activated sufficient shows differentially expressed genes are enriched in involved G protein Ca 2+signaling, ATP metabolism, regulating cytoskeleton reorganization cell homing. In summary, our data demonstrate major impact generation their ability respond stimulation, precipitate