Induction of Foxp3 demethylation increases regulatory CD4(+)CD25 (+) T cells and prevents the occurrence of diabetes in mice. Export

@article{citeulike:5999650, abstract = {CD4(+)CD25(+) regulatory T cells (Treg), a subpopulation of CD4(+) T cells, regulate immune responses. Foxp3 is a key transcription factor for the development and function of Treg cells. During T-cell activation in vitro, a DNA demethylation agent 5-Aza-2'-deoxycytydine (DAC) can induce Foxp3 expression in CD4(+)CD25(-) Foxp3(-) cells via altering methylation status of a conserved element in the 5'-untranslated region of the Foxp3 gene. However, the effects of this agent on the development of Foxp3(+) Treg cells in the thymus and in vivo are poorly understood. In the present study, a short-term treatment with a low dose of DAC significantly increased the ratios of thymic CD4(+)CD8(-) CD25(+) cells or CD4(+)CD8(-) Foxp3(+) cells to CD4(+)CD8(-) cells, and the total numbers of thymic CD4(+)CD8(-)Foxp3(+) Treg cells or CD4(+)CD8(-)CD25(+)Foxp3(+) Treg cells in the thymus in mice. DAC-treatment induced the Foxp3 expression and the significant demethylation of a CpG island in the first intron of the Foxp3 gene in CD4(+)CD8(-)CD25(+) cells predominantly. Furthermore, CD4(+)CD8(-)CD25(+) thymocytes in DAC-treated mice exhibited enhanced immunosuppressive function than those in control mice. In addition, DAC treatment in vivo was effective in improving the clinical course of diabetes in cyclophosphamide (CY)-potentiated non-obese diabetic mice (CY-NOD). Thus, the in vivo treatment with DAC can significantly promote the development of natural thymic CD4(+)CD25(+)Foxp3(+) Treg cells through Foxp3 demethylation, implicating a therapeutic application of DAC in patients suffering from autoimmune diseases.}, author = {Zheng, Qanhui and Xu, Yamei and Liu, Yanlong and Zhang, Baojun and Li, Xiaokun and Guo, Feng and Zhao, Yong}, citeulike-article-id = {5999650}, citeulike-linkout-0 = {http://dx.doi.org/10.1007/s00109-009-0530-8}, citeulike-linkout-1 = {http://view.ncbi.nlm.nih.gov/pubmed/19841877}, citeulike-linkout-2 = {http://www.hubmed.org/display.cgi?uids=19841877}, citeulike-linkout-3 = {http://www.springerlink.com/content/0640621007560k70}, day = {20}, doi = {10.1007/s00109-009-0530-8}, issn = {1432-1440}, journal = {Journal of molecular medicine (Berlin, Germany)}, keywords = {autoimmune\_diseases, epigenetics, foxp3, t1d, treg\_cells}, month = {October}, posted-at = {2009-10-24 14:44:40}, priority = {2}, title = {Induction of Foxp3 demethylation increases regulatory CD4(+)CD25 (+) T cells and prevents the occurrence of diabetes in mice.}, url = {http://dx.doi.org/10.1007/s00109-009-0530-8}, year = {2009} }

TY - JOUR ID - citeulike:5999650 L3 - citeulike-article-id:5999650 N2 - CD4(+)CD25(+) regulatory T cells (Treg), a subpopulation of CD4(+) T cells, regulate immune responses. Foxp3 is a key transcription factor for the development and function of Treg cells. During T-cell activation in vitro, a DNA demethylation agent 5-Aza-2'-deoxycytydine (DAC) can induce Foxp3 expression in CD4(+)CD25(-) Foxp3(-) cells via altering methylation status of a conserved element in the 5'-untranslated region of the Foxp3 gene. However, the effects of this agent on the development of Foxp3(+) Treg cells in the thymus and in vivo are poorly understood. In the present study, a short-term treatment with a low dose of DAC significantly increased the ratios of thymic CD4(+)CD8(-) CD25(+) cells or CD4(+)CD8(-) Foxp3(+) cells to CD4(+)CD8(-) cells, and the total numbers of thymic CD4(+)CD8(-)Foxp3(+) Treg cells or CD4(+)CD8(-)CD25(+)Foxp3(+) Treg cells in the thymus in mice. DAC-treatment induced the Foxp3 expression and the significant demethylation of a CpG island in the first intron of the Foxp3 gene in CD4(+)CD8(-)CD25(+) cells predominantly. Furthermore, CD4(+)CD8(-)CD25(+) thymocytes in DAC-treated mice exhibited enhanced immunosuppressive function than those in control mice. In addition, DAC treatment in vivo was effective in improving the clinical course of diabetes in cyclophosphamide (CY)-potentiated non-obese diabetic mice (CY-NOD). Thus, the in vivo treatment with DAC can significantly promote the development of natural thymic CD4(+)CD25(+)Foxp3(+) Treg cells through Foxp3 demethylation, implicating a therapeutic application of DAC in patients suffering from autoimmune diseases. JF - Journal of molecular medicine (Berlin, Germany) SN - 1432-1440 TI - Induction of Foxp3 demethylation increases regulatory CD4(+)CD25 (+) T cells and prevents the occurrence of diabetes in mice. KW - autoimmune_diseases KW - epigenetics KW - foxp3 KW - t1d KW - treg_cells AU - Zheng, Qanhui AU - Xu, Yamei AU - Liu, Yanlong AU - Zhang, Baojun AU - Li, Xiaokun AU - Guo, Feng AU - Zhao, Yong PY - 2009/10/20/ UR - http://dx.doi.org/10.1007/s00109-009-0530-8 ER -