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- W1603664764 abstract "Abstract Autoimmune pancreatitis (AIP) is a chronic inflammation of pancreas marked by high serum immunoglobulins and leukocytic infiltration. While the Il2-/- mice, which have reduced Treg levels, develop severe pancreatitis, the Foxp3-mutant Scurfy (Sf) mice, with a complete Treg-deficiency, are resistant to pancreatitis though they have a fatal multiorgan inflammation. Rendering Sf mice deficient for IL-2 (Sf.Il2-/-) abolished this resistance to AIP. We have shown that IL-2 is critical for the Th2 and not the Th1 response in the Sf mice. Thus, we hypothesized that a strong Th2 response in the Sf mice protects against AIP while a poor Th2 response due to IL-2 deficiency fails to suppress the disease. Indeed, Sf mice lacking IL-4 (Sf.Il4-/-) or STAT6 (Sf.Stat6-/-) developed severe AIP, while IFN-γ -deficient Sf mice (Sf.Ifng-/-) remained free from pancreatitis. Interestingly, all these mice had hyper-gammaglobulinemia and serum reactivity to carbonic anhydrase II. Our data further shows that lack of IL-2 or inadequate Th2 expression in the Sf mice causes an increase in the IFN-γ levels leading to upregulation of CXCR5, CXCR3 and CCR5 on the CD4+ T-cells and an increase in IP-10 and RANTES levels locally in the pancreas. The CD4+ T-cells then infiltrate the pancreas and form tertiary lymphoid follicles leading to AIP. We propose that although Treg-deficiency contributes to AIP, IL-2 regulates clinical manifestation of the disease in a Th2 dependent manner." @default.
- W1603664764 created "2016-06-24" @default.
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- W1603664764 date "2012-05-01" @default.
- W1603664764 modified "2023-10-18" @default.
- W1603664764 title "T-regulatory cell (Treg)-extrinsic role of IL-2 in protection against Autoimmune Pancreatitis (123.31)" @default.
- W1603664764 doi "https://doi.org/10.4049/jimmunol.188.supp.123.31" @default.
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