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Expression of activ...
Expression of activated Notch3 in transgenic mice enhances generation of T regulatory cells and protects against experimental autoimmune diabetes
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Anastasi, E (author)
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Campese, AF (author)
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Bellavia, D (author)
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Bulotta, A (author)
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Balestri, A (author)
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Pascucci, M (author)
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Checquolo, S (author)
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Gradini, R (author)
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- Lendahl, U (author)
- Karolinska Institutet
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Frati, L (author)
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Gulino, A (author)
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Di Mario, U (author)
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Screpanti, I (author)
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(creator_code:org_t)
- The American Association of Immunologists, 2003
- 2003
- English.
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In: Journal of immunology (Baltimore, Md. : 1950). - : The American Association of Immunologists. - 0022-1767 .- 1550-6606. ; 171:9, s. 4504-4511
- Related links:
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http://www.jimmunol....
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http://kipublication...
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https://doi.org/10.4...
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Abstract
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- 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.
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- By the author/editor
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Anastasi, E
-
Campese, AF
-
Bellavia, D
-
Bulotta, A
-
Balestri, A
-
Pascucci, M
-
show more...
-
Checquolo, S
-
Gradini, R
-
Lendahl, U
-
Frati, L
-
Gulino, A
-
Di Mario, U
-
Screpanti, I
-
show less...
- Articles in the publication
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Journal of immun ...
- By the university
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Karolinska Institutet