ORCID Profile
0000-0002-7983-6905
Current Organisation
San Raffale Scientific Institute
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Publisher: Routledge
Date: 09-01-2015
Publisher: American Diabetes Association
Date: 18-07-2011
DOI: 10.2337/DB10-1201
Abstract: The gut environment modulates the pathogenesis of type 1 diabetes (T1D), but how it affects autoimmunity toward pancreatic β-cells, a self-tissue located outside the intestine, is still unclear. In the small intestine, lamina propria dendritic cells (LPDCs) induce peripheral differentiation of FoxP3+ regulatory T (Treg) cells. We tested the hypothesis that the intestinal milieu impinges on human T1D by affecting differentiation of FoxP3+ Treg cells. We collected duodenal biopsies of 10 T1D patients, 16 healthy subjects, and 20 celiac in iduals and performed a fluorescent-activated cell sorter analysis to measure percentages of various immune cell subsets, including CD4+ and CD8+ T cells, NK cells, γδ T cells, CD103+CD11c+ LPDCs, and CD4+CD25+FoxP3+CD127− Treg cells. In parallel, we assessed the tolerogenic function (i.e., capacity to induce differentiation of FoxP3+ Treg cells) by LPDCs of T1D patients and control subjects. Our analysis revealed a significant reduction in the percentage of intestinal CD4+CD25+FoxP3+CD127− Treg cells in T1D patients compared with healthy subjects (P = 0.03) and celiac in iduals (P = 0.003). In addition, we found that LPDCs from T1D patients completely lacked their tolerogenic function they were unable to convert CD4+CD25− T cells into CD4+CD25+FoxP3+CD127− Treg cells. Our data indicate that T1D patients have a reduced number of intestinal FoxP3+ Treg cells as a result of their defective differentiation in the gut. These findings suggest that intestinal immune regulation is not only calibrated to tolerate commensal bacteria and food components but also is instrumental in maintaining immune tolerance toward pancreatic β-cells and preventing T1D.
Publisher: American Diabetes Association
Date: 17-10-2011
DOI: 10.2337/DB11-0090
Abstract: Autoimmune diseases, including type 1 diabetes, are thought to have a Th17-cell bias and/or a T-regulatory cell (Treg) defect. Understanding whether this is a hallmark of patients with type 1 diabetes is a crucial question that is still unsolved, largely due to the difficulties of accessing tissues targeted by the disease. We phenotypically and functionally characterized Th17 cells and Tregs residing in the pancreatic-draining lymph nodes (PLNs) of 19 patients with type 1 diabetes and 63 nondiabetic donors and those circulating in the peripheral blood of 14 type 1 diabetic patients and 11 healthy subjects. We found upregulation of Th17 immunity and functional defects in CD4+CD25bright Tregs in the PLNs of type 1 diabetic subjects but not in their peripheral blood. In addition, the proinsulin-specific Treg-mediated control was altered in the PLNs of diabetic patients. The dysfunctional Tregs isolated from diabetic subjects did not contain contaminant effector T cells and were all epigenetically imprinted to be suppressive, as defined by analysis of the Treg-specific demethylated region within the forkhead box P3 (FOXP3) locus. These data provide evidence for an unbalanced immune status in the PLNs of type 1 diabetic subjects, and treatments restoring the immune homeostasis in the target organ of these patients represent a potential therapeutic strategy.
Publisher: Public Library of Science (PLoS)
Date: 07-08-2014
No related grants have been discovered for Marina Scavini.