Expression of toll-like receptors in the pancreas of recent-onset fulminant type 1 diabetes

Saeko Shibasaki, Akihisa Imagawa, Sisko Tauriainen, Morio Iino, Maarit Oikarinen, Abiru Hitoshi, Keiji Tamaki, Hiroaki Seino, Katsuhiro Nishi, Izumi Takase, Yoshikatsu Okada, Sae Uno, Yuko Murase-Mishiba, Jungo Terasaki, Hideichi Makino, Iichiro Shimomura, Heikki Hyöty, Toshiaki Hanafusa

Research output: Contribution to journalArticlepeer-review

75 Citations (Scopus)

Abstract

Fulminant type 1 diabetes, established in 2000, is defined as a novel subtype of diabetes mellitus that results from remarkably acute and almost complete destruction of pancreatic beta cells at the disease onset. In this study, we aimed to clarify the pathogenesis of fulminant type 1 diabetes with special reference to insulitis and viral infection. We examined pancreatic autopsy samples from three patients who had died soon after the onset of disease and analyzed these by immunohistochemistry and in situ hybridization. The results were that both beta and alpha cell areas were significantly decreased in comparison with those of normal controls. Mean beta cell area of the patients just after the onset was only 0.00256 % while that of normal control was 1.745 %. Macrophages and T cells-but no natural killer cells-had infiltrated the islets and the exocrine pancreas. Although both of them had massively infiltrated, macrophages dominated islet infiltration and were detected in 92.6 % of the patients' islets. Toll-like receptor (TLR) 3, a sensor of viral components, was detected in 84.7±7.0 % of macrophages and 62.7±32.3 % of T cells (mean±SD) in all three patients. TLR7 and TLR9 were also detected in the pancreas of all three patients. Enterovirus RNA was detected in beta-cell positive islets in one of the three patients by in situ hybridization. In conclusion, our results suggest that macrophage-dominated insulitis rather than T cell autoimmunity contributes to beta cell destruction in fulminant type 1 diabetes.

Original languageEnglish
Pages (from-to)211-219
Number of pages9
JournalEndocrine journal
Volume57
Issue number3
DOIs
Publication statusPublished - 2010 Apr 2

Keywords

  • Enterovirus
  • Insulitis
  • Toll-like receptor

ASJC Scopus subject areas

  • Endocrinology, Diabetes and Metabolism
  • Endocrinology

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