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EnglishThymic-derived dysregulated tolerance has been suggested to occur in type 1 diabetes via impaired generation of CD4+CD25+ T regulatory cells, leading to autoimmune β cell destruction. In this study, we demonstrate that Notch3 expression is a characteristic feature of CD4 +CD25+ cells. Furthermore, streptozotocin-induced autoimmune diabetes fails to develop in transgenic mice carrying the constitutively active intracellular domain of Notch3 in thymocytes and T cells. The failure to develop the disease is associated with an increase of CD4 +CD25+ T regulatory cells, accumulating in lymphoid organs, in pancreas infiltrates and paralleled by increased expression of IL-4 and IL-10. Accordingly, CD4+ T cells from Notch3-transgenic mice inhibit the development of hyperglycemia and insulitis when injected into streptozotocin-treated wild-type mice and display in vitro suppressive activity. These observations, therefore, suggest that Notch3-mediated events regulate the expansion and function of T regulatory cells, leading to protection from experimental autoimmune diabetes and identify the Notch pathway as a potential target for therapeutic intervention in type 1 diabetes.
Expression of Activated Notch3 in Transgenic Mice Enhances Generation of T Regulatory Cells and Protects against Experimental Autoimmune Diabetes / Anastasi, Emanuela; Campese, Antonio Francesco; Bellavia, Diana; A., Bulotta; A., Balestri; M., Pascucci; Checquolo, Saula; Gradini, Roberto; U., Lendahl; Frati, Luigi; Gulino, Alberto; DI MARIO, Umberto; Screpanti, Isabella. - In: JOURNAL OF IMMUNOLOGY. - ISSN 0022-1767. - STAMPA. - 171:9(2003), pp. 4504-4511.
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| Titolo: | Expression of Activated Notch3 in Transgenic Mice Enhances Generation of T Regulatory Cells and Protects against Experimental Autoimmune Diabetes | |
| Autori: | ||
| Data di pubblicazione: | 2003 | |
| Rivista: | ||
| Citazione: | Expression of Activated Notch3 in Transgenic Mice Enhances Generation of T Regulatory Cells and Protects against Experimental Autoimmune Diabetes / Anastasi, Emanuela; Campese, Antonio Francesco; Bellavia, Diana; A., Bulotta; A., Balestri; M., Pascucci; Checquolo, Saula; Gradini, Roberto; U., Lendahl; Frati, Luigi; Gulino, Alberto; DI MARIO, Umberto; Screpanti, Isabella. - In: JOURNAL OF IMMUNOLOGY. - ISSN 0022-1767. - STAMPA. - 171:9(2003), pp. 4504-4511. | |
| Handle: | http://hdl.handle.net/11573/387826 | |
| Appartiene alla tipologia: | 01a Articolo in rivista |
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