Foxp3+ regulatory T cells (TR) are an immunosuppressive subset of CD4+ T cells that maintain homeostasis of the immune system. They are sustained by the interaction between the Major Histocompatibility Complex (MHC) molecules present on antigen presenting dendritic cells and the T Cell Receptor (TCR) expressed on TR cells that is specific for the MHC loaded with an antigenic peptide. Here, we show that in addition to MHC/TCR interaction, Connexin-43 (Cx43) expression by dendritic cells is required to maintain the TR cell population. CD11c+ dendritic cells represent a major subset of antigen presenting cells. Using flow cytometry, we have observed that mice which lack Cx43 expression in CD11c+ dendritic cells (Cx43DC-), have a lower percentage of TR cells which express lower levels of Foxp3. These mice showed increased incidence of dermatitis as they age, even though we show that their dendritic cells can efficiently present antigen to naive T cells using proliferation inhibition assay. The decrease in the proportion of TR cells were associated with an altered phenotype of these cells, demonstrated by lower expression of CD39 and higher expression of CD73, ectonucleotidases mediating TR cell immunosuppressive function. We propose that the presence of Cx43 on the surface of dendritic cells is required for effective communication between TR cells and dendritic cells so as to sustain TR cell homeostatic expansion and Foxp3 expression
