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J Immunol. 2011 Jul 1;187(1):248-57. doi: 10.4049/jimmunol.1003785. Epub 2011 Jun 3.

Connexin 43 signaling enhances the generation of Foxp3+ regulatory T cells.

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  • 1Center for Biotechnology and Genomic Medicine, Medical College of Georgia, Augusta, GA 30912, USA.


Despite their importance for the functioning of the immune system, thymic development and peripheral maintenance of Foxp3(+) regulatory T (T(R)) cells are poorly understood. We have found that connexin 43 (Cx43), expressed by thymic T(R) cells progenitors, supports T(R) development. Mice with deletion of the Cx43 gene induced in T cells produce only few T(R) cells and had increased proportion of activated T cells in the lymph nodes, suggesting impaired peripheral tolerance. Reduction of the T(R) cell numbers was accompanied by increased presence of CD4(+)CD25(+)GITR(+)Foxp3(-) T cells, which did not produce inflammatory cytokines and lost suppressor function. These results strongly argue that we have discovered a novel signaling pathway, controlled by Cx43, that enhances the generation of T(R) cells. We propose that a possible mechanism of Cx43 activity is by regulating Foxp3 expression in T(R) lineage cells.

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