Expression of Connexin-43 by CD11c+Dendritic Cells is Required for Maintaining CD4+Foxp3+ Regulatory T Cell Populcation

Immunosuppressive Foxp3+ Regulatory T cells (TR) are a subset of CD4+ T cells that maintain homeostasis of the immune system. They have been shown to be sustained by the interaction between MHC present on antigen presenting dendritic cells with the T Cell Receptor for antigen (TCR) that is expressed on TR cells. Here, we show that in addition to MHC/TCR interaction, Connexin-43 (Cx43) expression by dendritic cells is required to maintain the TR population. We have observed that mice that lack Connexin-43 expression on a major subset of antigen presenting cells- CD11c+ dendritic cells, have a lower percentage of TR cell population, which in turn also have a lower level of Foxp3 expression. These mice show increased incidence of dermatitis as they age. The dendritic cells from these mice efficiently presents antigen to effector T cells. The changes of TR subset were associated with an altered phenotype of these cells, demonstrated by lower expression of CD39, an ectonucleotidase which is involved in its 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 which is essential to sustain TR cell proliferation and Foxp3 expression. ; https://digitalcommons.odu.edu/sciences_achievement/1016/thumbnail.jpg