Expression of chemokines, CXC chemokine ligand 10 (CXCL10) and CXCR3 in the inflamed islets of patients with recent-onset autoimmune type 1 diabetes.
The aim of this study is to present direct evidence for the involvement of CXC chemokine ligand 10 (CXCL10) and CXCR3 in human autoimmune type 1 diabetes. We examined five patients with recent-onset type 1 diabetes and five control subjects without diabetes. Islet cell antibodies or GAD antibodies or both were detected in all five patients. We used double-immunofluorescence to detect the expression of CXCL10 and CXCR3 (the receptor of CXCL10). CXCL10 was detected in the islets of all five patients. Almost all (84.2 ± 10.3 %, mean ± SD) CXCL10-positive cells were insulin-positive in the islet area. CXCL10-positive cells with glucagons, somatostatins or pancreatic polypeptides were not detected at all. CXCL10 expression was not seen in any islet without beta cells. CXCR3 was detected in the islet areas of all five patients. Almost all (80.3 ± 13.4 %, mean ± SD) CXCR3-positive cells were CD3-positive T cells. Our study showed that CXCL10 was expressed in the remaining beta cells, and the infiltrating T cells expressed CXCR3, in pancreatic islets of patients with recent-onset type 1 diabetes. The interaction of CXCL10 and CXCR3 would contribute to the selective destruction of beta cells in the development of type 1 diabetes.
Department of Metabolic Medicine, Graduate School of Medicine, Osaka University, 2-2-B5 Yamadaoka, Suita, Japan.
Sae
S
Uno
Akihisa
A
Imagawa
Kenji
K
Saisho
Kohei
K
Okita
Hiromi
H
Iwahashi
Toshiaki
T
Hanafusa
Iichiro
I
Shimomura
D001706:Biopsy; D054357:Chemokine CXCL10 / Q000096:biosynthesis*; D003922:Diabetes Mellitus, Type 1 / Q000276:immunology* / Q000473:pathology; D006801:Humans; D007150:Immunohistochemistry; D007515:Islets of Langerhans / Q000276:immunology* / Q000473:pathology; D054367:Receptors, CXCR3 / Q000096:biosynthesis*; D055815:Young Adult
C114753:CXCL10 protein, human; C515187:CXCR3 protein, human; D054357:Chemokine CXCL10; D054367:Receptors, CXCR3