Article

Generalized multi-organ autoimmunity in CCR7-deficient mice.

Institute of Immunology, Hannover Medical School, Hannover, Germany.
European Journal of Immunology (impact factor: 5.1). 04/2007; 37(3):613-22. DOI:10.1002/eji.200636656 pp.613-22
Source: PubMed

ABSTRACT Development of autoimmunity is a multi-factorial process involving genetic predisposition as well as environmental and stochastic factors. Although the mechanisms responsible for the initiation of autoimmunity remain only partially understood, several studies have demonstrated that genetic predisposition plays a major role in this process. In the present study, we analyzed the influence of CCR7 signaling in the development of autoimmunity, because this chemokine receptor is essentially involved in the functional organization of thymus architecture. We demonstrate that CCR7-deficient mice are prone to develop generalized multi-organ autoimmunity. The autoimmune phenotype of CCR7-/- mice encompasses the presence of lymphocyte infiltrates in several peripheral organs, circulating autoantibodies against a multitude of tissue-specific antigens and IgG deposition on renal glomeruli. Additionally, CCR7-deficient mice show increased susceptibility to streptozotocin-induced diabetes and spontaneously display signs of chronic autoimmune renal disease. Thus, this study identifies CCR7 as a genetic factor involved in the regulation of autoimmunity.

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Keywords

autoantibodies
 
autoimmune phenotype
 
autoimmunity
 
CCR7-/- mice encompasses
 
CCR7-deficient mice
 
chemokine receptor
 
chronic autoimmune renal disease
 
functional organization
 
generalized multi-organ autoimmunity
 
genetic factor
 
genetic predisposition
 
lymphocyte infiltrates
 
major role
 
multi-factorial process
 
peripheral organs
 
renal glomeruli
 
spontaneously display signs
 
stochastic factors
 
tissue-specific antigens