Involvement of eotaxin, eosinophils, and pancreatic predisposition in development of type 1 diabetes mellitus in the BioBreeding rat. J Immunol 2004 Dec 01;173(11):6993-7002
Date
11/24/2004Pubmed ID
15557196DOI
10.4049/jimmunol.173.11.6993Scopus ID
2-s2.0-9144238154 (requires institutional sign-in at Scopus site) 52 CitationsAbstract
Allergy and autoimmunity are both examples of deregulated immunity characterized by inflammation and injury of targeted tissues that have until recently been considered disparate disease processes. However, recent findings have implicated mast cells, in coordination with granulocytes and other immune effector cells, in the pathology of these two disorders. The BioBreeding (BB) DRlyp/lyp rat develops an autoimmune insulin-dependent diabetes similar to human type 1 diabetes mellitus (T1DM), whereas the BBDR+/+ rat does not. To better understand immune processes during development of T1DM, gene expression profiling at day (d) 40 (before insulitis) and d65 (before disease onset) was conducted on pancreatic lymph nodes of DRlyp/lyp, DR+/+, and Wistar-Furth (WF) rats. The eosinophil-recruiting chemokine, eotaxin, and the high-affinity IgE receptor (FcepsilonRI) were up-regulated >5-fold in d65 DRlyp/lyp vs d65 DR+/+ pancreatic lymph nodes by microarray (p < 0.05) and quantitative RT-PCR studies (p < 0.05). DR+/+, WF, and d40 DRlyp/lyp animals possessed normal pancreatic histology; however, d65 DRlyp/lyp animals possessed eosinophilic insulitis. Therefore, immunohistochemistry for pancreatic eotaxin expression was conducted, revealing positive staining of d65 DRlyp/lyp islets. Islets of d65 DR+/+ rats also stained positively, consistent with underlying diabetic predisposition in the BB lineage, whereas WF islets did not. Other differentially expressed transcripts included those associated with eosinophils, mast cells, and lymphocytes. These data support an important role for these inflammatory mediators in BB rat T1DM and suggest that the lymphopenia due to the Ian5/(lyp) mutation may result in a deregulation of cells involved in insulitis and beta cell destruction.
Author List
Hessner MJ, Wang X, Meyer L, Geoffrey R, Jia S, Fuller J, Lernmark A, Ghosh SAuthor
Martin J. Hessner PhD Professor in the Pediatrics department at Medical College of WisconsinMESH terms used to index this publication - Major topics in bold
AnimalsCell Movement
Chemokine CCL11
Chemokines, CC
Diabetes Mellitus, Type 1
Eosinophils
Gene Expression Profiling
Genetic Predisposition to Disease
Immunohistochemistry
Islets of Langerhans
Lymph Nodes
Mast Cells
Oligonucleotide Array Sequence Analysis
Pancreas
Prediabetic State
Protein Tyrosine Phosphatase, Non-Receptor Type 1
Protein Tyrosine Phosphatase, Non-Receptor Type 22
Protein Tyrosine Phosphatases
Rats
Rats, Inbred BB
Rats, Inbred WF
Receptors, IgE
Reverse Transcriptase Polymerase Chain Reaction