Transgenic Expression of Murine Chemokine Decoy Receptor D6 by Islets Reveals the Role of Inflammatory CC Chemokines in the Development of Autoimmune Diabetes in NOD Mice

Overview

Journal Diabetologia

Specialty Endocrinology

Date 2011 May 6

PMID 21544515

Citations 7

Authors

G-J Lin

S-H Huang

Y-W Chen

D-Y Hueng

W-T Chia

M-W Chien

B L Yen

H-K Sytwu

Affiliations

Soon will be listed here.

Abstract

Aims/hypothesis: Autoimmune diabetes results from a progressive destruction of insulin-producing beta cells in the pancreatic islets by chemokine-attracted lymphocytes. Because islet cells in NOD mice produce chemokines during the development of autoimmune diabetes, we investigated the role of inflammatory CC chemokines in disease progression in these mice.

Methods: We generated a transgenic NOD mouse model that overproduces the inflammatory CC chemokine decoy receptor D6 in pancreatic islets.

Results: The frequency of diabetes and insulitis scores of transgenic mice were decreased significantly, compared with non-transgenic control littermates. Transgenic expression of D6 (also known as Ccbp2) did not affect systemic lymphocyte development or alter: (1) the T cell subsets such as T helper (Th)1, Th2 and T regulatory cells; or (2) antigen-presenting cells such as dendritic cells or macrophages. The percentages and numbers of T and B lymphocytes were decreased significantly in the pancreas. Activation status, autoantigen-specific proliferation and diabetogenicity of lymphocytes were also markedly reduced.

Conclusions/interpretation: Inflammatory CC chemokines play a critical role in the development of autoimmune diabetes. Transgenic expression of D6 in pancreatic islets of NOD mice reduced this pathogenic process by suppressing activation of autoreactive lymphocytes and by reducing migration of lymphocytes to the pancreas.

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