TY - JOUR
T1 - Connexin 43 signaling enhances the generation of Foxp3+ regulatory T cells
AU - Kuczma, Michal
AU - Lee, Jeffrey R.
AU - Kraj, Piotr
PY - 2011/7/1
Y1 - 2011/7/1
N2 - 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 TR cells progenitors, supports T R development. Mice with deletion of the Cx43 gene induced in T cells produce only few TR cells and had increased proportion of activated T cells in the lymph nodes, suggesting impaired peripheral tolerance. Reduction of the TR 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 TR cells. We propose that a possible mechanism of Cx43 activity is by regulating Foxp3 expression in TR lineage cells.
AB - 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 TR cells progenitors, supports T R development. Mice with deletion of the Cx43 gene induced in T cells produce only few TR cells and had increased proportion of activated T cells in the lymph nodes, suggesting impaired peripheral tolerance. Reduction of the TR 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 TR cells. We propose that a possible mechanism of Cx43 activity is by regulating Foxp3 expression in TR lineage cells.
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U2 - 10.4049/jimmunol.1003785
DO - 10.4049/jimmunol.1003785
M3 - Article
C2 - 21642545
AN - SCOPUS:79960418125
SN - 0022-1767
VL - 187
SP - 248
EP - 257
JO - Journal of Immunology
JF - Journal of Immunology
IS - 1
ER -