Expression of chemokines, CXC chemokine ligand 10 (CXCL10) and CXCR3 in the inflamed islets of patients with recent-onset autoimmune type 1 diabetes

被引：54
作者：
Uno, Sae [1 ]
Imagawa, Akihisa [1 ]
Saisho, Kenji [1 ]
Okita, Kohei [1 ]
Iwahashi, Hiromi [1 ]
Hanafusa, Toshiaki [2 ]
Shimomura, Iichiro [1 ]
机构：
[1] Osaka Univ, Grad Sch Med, Dept Metab Med, Suita, Osaka 5650871, Japan
[2] Osaka Med Coll, Dept Internal Med 1, Takatsuki, Osaka 5698686, Japan
来源：
ENDOCRINE JOURNAL | 2010年 / 57卷 / 11期
关键词：
Biopsy; Chemokine; IP-10; CXCL10; CXCR3; BETA-CELLS; INDUCIBLE PROTEIN-10; INTERFERON-GAMMA; INFILTRATION; INFLAMMATION; INSULITIS; ADHESION; MELLITUS;
D O I：
10.1507/endocrj.K10E-076
中图分类号：
R5 [内科学];
学科分类号：
1002 ; 100201 ;
摘要：
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.
引用
收藏
页码：991 / 996
页数：6
相关论文
共 18 条
  • [1] Type 1 diabetes: new perspectives on disease pathogenesis and treatment
    Atkinson, MA
    Eisenbarth, GS
    [J]. LANCET, 2001, 358 (9277) : 221 - 229
  • [2] Induction of the chemokine interferon-γ-inducible protein-10 in human pancreatic islets during enterovirus infection
    Berg, A. -K.
    Korsgren, O.
    Frisk, G.
    [J]. DIABETOLOGIA, 2006, 49 (11) : 2697 - 2703
  • [3] β cells are responsible for CXCR3-mediated T-cell infiltration in insulitis
    Frigerio, S
    Junt, T
    Lu, B
    Gerard, C
    Zumsteg, U
    Holländer, GA
    Piali, L
    [J]. NATURE MEDICINE, 2002, 8 (12) : 1414 - 1420
  • [4] Homing of human autoreactive T cells into pancreatic tissue of NOD-scid mice
    Halteren, AGS
    Kardol, MJ
    Mulder, A
    Roep, BO
    [J]. DIABETOLOGIA, 2005, 48 (01) : 75 - 82
  • [5] MONONUCLEAR CELL INFILTRATION AND ITS RELATION TO THE EXPRESSION OF MAJOR HISTOCOMPATIBILITY COMPLEX ANTIGENS AND ADHESION MOLECULES IN PANCREAS BIOPSY SPECIMENS FROM NEWLY-DIAGNOSED INSULIN-DEPENDENT DIABETES-MELLITUS PATIENTS
    ITOH, N
    HANAFUSA, T
    MIYAZAKI, A
    MIYAGAWA, J
    YAMAGATA, K
    YAMAMOTO, K
    WAGURI, M
    IMAGAWA, A
    TAMURA, S
    INADA, M
    KAWATA, S
    TARUI, S
    KONO, N
    MATSUZAWA, Y
    [J]. JOURNAL OF CLINICAL INVESTIGATION, 1993, 92 (05) : 2313 - 2322
  • [6] Double-stranded RNA cooperates with interferon-γ and IL-1β to induce both chemokine expression and nuclear factor-κB-dependent apoptosis in pancreatic β-cells:: Potential mechanisms for viral-induced insulitis and β-cell death in type 1 diabetes mellitus
    Liu, DB
    Cardozo, AK
    Darville, MI
    Eizirik, DL
    [J]. ENDOCRINOLOGY, 2002, 143 (04) : 1225 - 1234
  • [7] The chemokine receptors CXCR3 and CCR5 mark subsets of T cells associated with certain inflammatory reactions
    Qin, SX
    Rottman, JB
    Myers, P
    Kassam, N
    Weinblatt, M
    Loetscher, M
    Koch, AE
    Moser, B
    Mackay, CR
    [J]. JOURNAL OF CLINICAL INVESTIGATION, 1998, 101 (04) : 746 - 754
  • [8] RABINOVITCH A, 1995, J IMMUNOL, V154, P4874
  • [9] Islet-specific expression of CXCL10 causes spontaneous islet infiltration and accelerates diabetes development
    Rhode, A
    Pauza, ME
    Barral, AM
    Rodrigo, E
    Oldstone, MBA
    von Herrath, MG
    Christen, U
    [J]. JOURNAL OF IMMUNOLOGY, 2005, 175 (06) : 3516 - 3524
  • [10] Islet inflammation and CXCL10 in recent-onset type 1 diabetes
    Roep, B. O.
    Kleijwegt, F. S.
    van Halteren, A. G. S.
    Bonato, V.
    Boggi, U.
    Vendrame, F.
    Marchetti, P.
    Dotta, F.
    [J]. CLINICAL AND EXPERIMENTAL IMMUNOLOGY, 2010, 159 (03) : 338 - 343
12