Characterization of CXCL10 expression pattern in pancreatic islets of NOD mice and type 1 diabetic patients: a new role for alpha-cells in T-lymphocytes recruitment

This abstract has open access
Abstract Summary

Background: in type 1 diabetes (T1D), the chemokine CXCL10 recruits autoreactive T-lymphocytes in pancreatic islets, contributing to beta-cells destruction. CXCL10 is expressed by murine and human pancreatic islets in autoimmune diabetes, however the specific expression pattern has not been elucidated yet. Our purpose was to clarify pancreatic CXCL10 expression, both in NOD mice and T1D patients.

Methods: we analyzed pancreatic sections from 4 C57Bl/6J 8 weeks(w), 3 C57Bl/6J 15-20 w, 4 NOD-SCID 2-3 w, 4 NOD normoglycemic (NG) 22 w, 4 NOD recent diabetic (RD) 12-21 w old mice, 6 new-onset T1D patients participating in Diabetes Virus Detection (DiViD) study and 3 non-diabetic organ donors from European Network for Pancreatic Organ Donors with Diabetes (EUnPOD). Immunofluorescence, confocal microscopy analysis and colocalization analysis insulin-CXCL10 (INS-CXCL10) and glucagon-CXCL10 (GCG-CXCL10) were performed. In mice, total CXCL10 positive volume was analyzed and normalized per islet volume; CXCL10 expression was correlated to lymphocytic infiltrates area.

Results: CXCL10 was expressed in pancreatic islets of NG and RD NOD but not in C57Bl/6J and NOD-SCID mice. GCG-CXCL10 colocalization rate (CR) was increased vs INS-CXCL10 (p<0.01) in RD NOD mice. INS-CXCL10 CR was similar between NG and RD NOD, GCG-CXCL10 was increased in RD vs NG NOD mice (p<0.001). CXCL10 positive volume was increased in RD vs NG NOD mice (p<0.01) and positively correlated to lymphocytic infiltrates area (r=0.44, p=0.02). CXCL10 was expressed in pancreatic islets of T1D patients but not in non-diabetic donors. GCG-CXCL10 CR was increased vs INS-CXCL10 (p=0.003) and was similar in insulin-containing vs -deficient islets, suggesting that CXCL10 expression in alpha-cells is not driven by residual beta-cells. The preferential expression of CXCL10  by alpha-cells, both in NOD mice and T1D patients, suggests a new role for alpha-cells in the recruitment of autoreactive T-lymphocytes in pancreatic islets and a primary function in beta-cell damage.

Submission ID :
IDS6276
Submission Type
Abstract Topics
Diabetes Unit, Department of Medicine, Surgery and Neuroscience, University of Siena and Fondazione Umberto Di Mario ONLUS c/o Toscana Life Science, Siena, Italy
Oslo University Hospital, Oslo, Norway
Laboratory of Experimental Medicine, University of Leuven, Belgium
Dept. of Clinical and Experimental Medicine, University of Pisa, Italy.
Laboratory of Experimental Medicine, University of Leuven, Belgium
Diabetes Unit Department of Medical Science, Surgery and Neuroscience, University of Siena, Italy; Umberto Di Mario Foundation ONLUS, Toscana Life Sciences, Siena
Dept. of Clinical and Experimental Medicine, University of Pisa, Italy
Oslo University Hospital, Oslo, Norway
Diabetes Unit, Department of Medicine, Surgery and Neuroscience, University of Siena and Fondazione Umberto Di Mario ONLUS c/o Toscana Life Science, Siena, Italy
Diabetes Unit, Dept. of Medicine, Surgery and Neuroscience, University of Siena; Umberto Di Mario Foundation ONLUS, Toscana Life Sciences, Siena, Italy

Abstracts With Same Type

Submission ID
Submission Title
Submission Topic
Submission Type
Primary Author
7 visits

KEY DATES

Event dates:
Thursday 25 October - Monday 29 October 2018

Abstract submission deadline:
Monday 14 May 2018

Abstract notification:
July 2018

Early registration deadline:
Monday 3 September 2018

Registration deadline:
Monday 15 October 2018

Contact
British Society for Immunology
+44 (0)20 3019 5901
congress@immunology.org