Low gene expression levels of activating receptors of natural killer cells (NKG2E and CD94) in patients with fulminant type 1 diabetes.

Abstract

Fulminant type 1 diabetes is an independent subtype of type 1 diabetes characterized by extremely rapid onset and absence of islet-related autoantibodies. However, detailed pathophysiology of this subtype is poorly understood. In this study, a comprehensive approach was applied to understand the pathogenesis of fulminant type 1 diabetes. We determined the genes that were differentially expressed in fulminant type 1 diabetes compared with type 1A diabetes and healthy control, using gene expression microarray in peripheral blood cells. Using volcano plot analysis, we found reduced expression of killer cell lectin-like receptor subfamily C, member 3 (KLRC3) which encodes NKG2E, a natural killer (NK) cell activating receptor, in fulminant type 1 diabetes, compared with healthy controls. This difference was confirmed by real-time RT-PCR among NK-enriched cells. The expression of KLRD1 (CD94), which forms heterodimer with NKG2E (KLRC3), was also reduced in NK-enriched cells in fulminant type 1 diabetes. Furthermore, flow cytometry showed significantly lower proportion of NK cells among peripheral blood mononuclear cells (PBMCs) in fulminant type 1 diabetes than in healthy controls. In patients with fulminant type 1 diabetes, the relative proportion of NK cells correlated significantly with the time period between onset of fever to the appearance of hyperglycemic-related symptoms. We conclude the presence of reduced NK activating receptor gene expression and low proportion of NK cells in fulminant type 1 diabetes.

• Authors: Shinsuke Nakata, Akihisa Imagawa, Yugo Miyata, Atsushi Yoshikawa, Junji Kozawa, Kohei Okita, Tohru Funahashi, Seiji Nakamura, Kenichi Matsubara, Hiromi Iwahashi, Iichiro Shimomura
• Journal: Immunology letters (Immunol Lett) 2013 Nov-Dec Vol. 156 Issue 1-2 Pg. 149-55 ISSN: 1879-0542 [Electronic] Netherlands
• PMID: 24177169 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2013 Elsevier B.V. All rights reserved.

Chemical References

• KLRC3 protein, human
• KLRD1 protein, human
• NK Cell Lectin-Like Receptor Subfamily C
• NK Cell Lectin-Like Receptor Subfamily D

Topics

• Adult
• Diabetes Mellitus, Type 1 (genetics, immunology, metabolism)
• Female
• Flow Cytometry
• Humans
• Killer Cells, Natural (immunology, metabolism)
• Leukocytes, Mononuclear (immunology, metabolism)
• Male
• NK Cell Lectin-Like Receptor Subfamily C (genetics, immunology, metabolism)
• NK Cell Lectin-Like Receptor Subfamily D (genetics, immunology, metabolism)
• Oligonucleotide Array Sequence Analysis
• Reverse Transcriptase Polymerase Chain Reaction
• Transcriptome (genetics, immunology)