Macrophages and Dendritic Cells Infiltrating Islets with or Without Beta Cells Produce Tumour Necrosis Factor-alpha in Patients with Recent-onset Type 1 Diabetes

Overview

Journal Diabetologia

Specialty Endocrinology

Date 2007 Jan 16

PMID 17221211

Citations 61

Authors

S Uno

A Imagawa

K Okita

K Sayama

M Moriwaki

H Iwahashi

K Yamagata

S Tamura

Y Matsuzawa

T Hanafusa

J Miyagawa

I Shimomura

Affiliations

Soon will be listed here.

Abstract

Aims/hypothesis: Type 1A diabetes results from autoimmune destruction of pancreatic beta cells. We examined the involvement of TNF-alpha and IL-1beta, as well as of T cells, macrophages and dendritic cells, in the destruction of beta cells in patients with recent-onset type 1 diabetes.

Materials And Methods: We obtained pancreatic biopsy specimens from six patients with recent-onset type 1 diabetes and analysed these by immunohistochemistry.

Results: T cell infiltration was less common in islets without beta cells (12.5 [0-33.3]%) than in those with beta cells (46.0 [17.4-83.3]%), while macrophages and dendritic cells showed a similar extent of infiltration into islets both with or without beta cells. TNF-alpha was detected in 25.0 (4.3-46.9)% of macrophages and 11.8 (0-40.0)% of dendritic cells infiltrating the islets in samples from each patient, but not at all in T cells. IL-1beta was detected in 1.8 (0-11.3)% of T cells infiltrating the islets with beta cells, while it was found in 19.2 (0-35.3)% of macrophages or 10.7 (0-31.3)% of dendritic cells infiltrating the islets in samples from each patient (all values median [range]).

Conclusions/interpretation: Macrophages and dendritic cells infiltrate the islets and produce inflammatory cytokines (TNF-alpha and IL-1beta) during the development of type 1A diabetes.

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References

Cailleau C, Diu-Hercend A, Ruuth E, Westwood R, Carnaud C . Treatment with neutralizing antibodies specific for IL-1beta prevents cyclophosphamide-induced diabetes in nonobese diabetic mice. Diabetes. 1997; 46(6):937-40. DOI: 10.2337/diab.46.6.937. View

Alberti K, Zimmet P . Definition, diagnosis and classification of diabetes mellitus and its complications. Part 1: diagnosis and classification of diabetes mellitus provisional report of a WHO consultation. Diabet Med. 1998; 15(7):539-53. DOI: 10.1002/(SICI)1096-9136(199807)15:7<539::AID-DIA668>3.0.CO;2-S. View

Nakayama M, Abiru N, Moriyama H, Babaya N, Liu E, Miao D . Prime role for an insulin epitope in the development of type 1 diabetes in NOD mice. Nature. 2005; 435(7039):220-3. PMC: 1364531. DOI: 10.1038/nature03523. View

Corbett J, Wang J, Sweetland M, Lancaster Jr J, McDaniel M . Interleukin 1 beta induces the formation of nitric oxide by beta-cells purified from rodent islets of Langerhans. Evidence for the beta-cell as a source and site of action of nitric oxide. J Clin Invest. 1992; 90(6):2384-91. PMC: 443394. DOI: 10.1172/JCI116129. View

Sandberg J, Eizirik D, Sandler S . IL-1 receptor antagonist inhibits recurrence of disease after syngeneic pancreatic islet transplantation to spontaneously diabetic non-obese diabetic (NOD) mice. Clin Exp Immunol. 1997; 108(2):314-7. PMC: 1904642. DOI: 10.1046/j.1365-2249.1997.3771275.x. View

Yamagata K, Nakajima H, Tomita K, Itoh N, Miyagawa J, Hamaguchi T . Dominant TCR alpha-chain clonotypes and interferon-gamma are expressed in the pancreas of patients with recent-onset insulin-dependent diabetes mellitus. Diabetes Res Clin Pract. 1996; 34(1):37-46. DOI: 10.1016/s0168-8227(96)01328-9. View

Iwahashi H, Hanafusa T, Eguchi Y, Nakajima H, Miyagawa J, Itoh N . Cytokine-induced apoptotic cell death in a mouse pancreatic beta-cell line: inhibition by Bcl-2. Diabetologia. 1996; 39(5):530-6. DOI: 10.1007/BF00403299. View

Stassi G, Todaro M, Richiusa P, Giordano M, Mattina A, Sbriglia M . Expression of apoptosis-inducing CD95 (Fas/Apo-1) on human beta-cells sorted by flow-cytometry and cultured in vitro. Transplant Proc. 1995; 27(6):3271-5. View

Yang X, Tisch R, Singer S, Cao Z, Liblau R, Schreiber R . Effect of tumor necrosis factor alpha on insulin-dependent diabetes mellitus in NOD mice. I. The early development of autoimmunity and the diabetogenic process. J Exp Med. 1994; 180(3):995-1004. PMC: 2191653. DOI: 10.1084/jem.180.3.995. View

10.

Thomas H, Darwiche R, Corbett J, Kay T . Evidence that beta cell death in the nonobese diabetic mouse is Fas independent. J Immunol. 1999; 163(3):1562-9. View

11.

Hanafusa T, Miyazaki A, Miyagawa J, Tamura S, Inada M, Yamada K . Examination of islets in the pancreas biopsy specimens from newly diagnosed type 1 (insulin-dependent) diabetic patients. Diabetologia. 1990; 33(2):105-11. DOI: 10.1007/BF00401048. View

12.

Itoh N, Hanafusa T, Miyazaki A, Miyagawa J, Yamagata K, Yamamoto K . 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. J Clin Invest. 1993; 92(5):2313-22. PMC: 288412. DOI: 10.1172/JCI116835. View

13.

Dahlen E, Dawe K, Ohlsson L, Hedlund G . Dendritic cells and macrophages are the first and major producers of TNF-alpha in pancreatic islets in the nonobese diabetic mouse. J Immunol. 1998; 160(7):3585-93. View

14.

Imagawa A, Hanafusa T, Tamura S, Moriwaki M, Itoh N, Yamamoto K . Pancreatic biopsy as a procedure for detecting in situ autoimmune phenomena in type 1 diabetes: close correlation between serological markers and histological evidence of cellular autoimmunity. Diabetes. 2001; 50(6):1269-73. DOI: 10.2337/diabetes.50.6.1269. View

15.

Calafiore R, Pietropaolo M, Basta G, Falorni A, Picchio M, Brunetti P . Pancreatic beta-cell destruction in non-obese diabetic mice. Metabolism. 1993; 42(7):854-9. DOI: 10.1016/0026-0495(93)90059-w. View

16.

Moriwaki M, Itoh N, Miyagawa J, Yamamoto K, Imagawa A, Yamagata K . Fas and Fas ligand expression in inflamed islets in pancreas sections of patients with recent-onset Type I diabetes mellitus. Diabetologia. 1999; 42(11):1332-40. DOI: 10.1007/s001250051446. View

17.

Eisenbarth G . Type I diabetes mellitus. A chronic autoimmune disease. N Engl J Med. 1986; 314(21):1360-8. DOI: 10.1056/NEJM198605223142106. View

18.

Thomas H, Irawaty W, Darwiche R, Brodnicki T, Santamaria P, Allison J . IL-1 receptor deficiency slows progression to diabetes in the NOD mouse. Diabetes. 2003; 53(1):113-21. DOI: 10.2337/diabetes.53.1.113. View

19.

Banchereau J, Steinman R . Dendritic cells and the control of immunity. Nature. 1998; 392(6673):245-52. DOI: 10.1038/32588. View

20.

Jiang Z, Woda B . Cytokine gene expression in the islets of the diabetic Biobreeding/Worcester rat. J Immunol. 1991; 146(9):2990-4. View