title: Connexin 43 signaling enhances the generation of Foxp3+ regulatory T cells.
abstract: 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.
authors.affiliation: Center for Biotechnology and Genomic Medicine, Medical College of Georgia, Augusta, GA 30912, USA.
authors.forename: Michal
authors.initials: M
authors.lastname: Kuczma
authors.forename: Jeffrey R
authors.initials: JR
authors.lastname: Lee
authors.forename: Piotr
authors.initials: P
authors.lastname: Kraj
mesh_terms: D000818:Animals; D002454:Cell Differentiation / Q000235:genetics / Q000276:immunology*; D045744:Cell Line, Tumor; D019070:Cell Lineage / Q000235:genetics / Q000276:immunology; D002478:Cells, Cultured; D018031:Connexin 43 / Q000096:biosynthesis / Q000235:genetics / Q000502:physiology*; D051858:Forkhead Transcription Factors / Q000096:biosynthesis*; D005786:Gene Expression Regulation / Q000276:immunology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008822:Mice, Transgenic; D011828:Radiation Chimera / Q000276:immunology; D015398:Signal Transduction / Q000235:genetics / Q000276:immunology*; D050378:T-Lymphocytes, Regulatory / Q000166:cytology / Q000276:immunology* / Q000378:metabolism*; D015854:Up-Regulation / Q000235:genetics / Q000276:immunology*
chemical_list: D018031:Connexin 43; C418974:FOXP3 protein, human; D051858:Forkhead Transcription Factors; C500216:GJA1 protein, human