Sökning: onr:"swepub:oai:prod.swepub.kib.ki.se:1946823" >
Expression of activ...
Abstract
Ämnesord
Stäng
- Thymic-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.
Publikations- och innehållstyp
- ref (ämneskategori)
- art (ämneskategori)
Hitta via bibliotek
Till lärosätets databas
- Av författaren/redakt...
-
Anastasi, E
-
Campese, AF
-
Bellavia, D
-
Bulotta, A
-
Balestri, A
-
Pascucci, M
-
visa fler...
-
Checquolo, S
-
Gradini, R
-
Lendahl, U
-
Frati, L
-
Gulino, A
-
Di Mario, U
-
Screpanti, I
-
visa färre...
- Artiklar i publikationen
-
Journal of immun ...
- Av lärosätet
-
Karolinska Institutet