title: CCR7 directs the recruitment of T cells into inflamed pancreatic islets of nonobese diabetic (NOD) mice.
abstract: Type 1 diabetes (T1D) is a T cell-mediated autoimmune disease characterized by the destruction of insulin-producing β cells in the pancreatic islets. The migration of T cells from blood vessels into pancreas is critical for the development of islet inflammation and β cell destruction in T1D. To define the roles of C-C chemokine receptor type 7 (CCR7) in recruitment of T cells into islets, we used laser capture microdissection to isolate tissue from inflamed islets of nonobese diabetic (NOD) mice and uninflamed islets of BALB/c and young NOD mice. RT-PCR analyses detected mRNAs for CCR7 and its chemokine ligands CCL19 (ELC; MIP-3β) and CCL21 (SLC) in captures from inflamed, but not from uninflamed, islets. Immunohistology studies revealed that high endothelial venules in inflamed islets co-express CCL21 protein and MAdCAM-1 (an adhesion molecule that recruits lymphocytes into islets). Desensitization of lymphocyte CCR7 blocked about 75 % of T cell migration from the bloodstream into inflamed islets, but had no effect on B cell migration into islets. These results indicate that CCR7 and its ligands are important in the recruitment of T cells into inflamed islets and thus in the pathogenesis of T1D.
authors.affiliation: Department of Pathology, Stanford University School of Medicine, Stanford, CA, 94305-5324, USA.
authors.forename: Zhongyan
authors.initials: Z
authors.lastname: Shan
authors.forename: Baohui
authors.initials: B
authors.lastname: Xu
authors.forename: Anna
authors.initials: A
authors.lastname: Mikulowska-Mennis
authors.forename: Sara A
authors.initials: SA
authors.lastname: Michie
mesh_terms: D000818:Animals; D000954:Antigens, Surface / Q000235:genetics / Q000378:metabolism; D015815:Cell Adhesion Molecules / Q000235:genetics / Q000378:metabolism; D002465:Cell Movement / Q000235:genetics / Q000276:immunology; D054415:Chemokine CCL19 / Q000235:genetics / Q000378:metabolism; D054421:Chemokine CCL21 / Q000235:genetics / Q000378:metabolism; D004195:Disease Models, Animal; D005260:Female; D015870:Gene Expression; D007515:Islets of Langerhans / Q000276:immunology* / Q000378:metabolism* / Q000473:pathology; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism; D051379:Mice; D016688:Mice, Inbred NOD; D009088:Mucoproteins; D010195:Pancreatitis / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D054400:Receptors, CCR7 / Q000235:genetics / Q000378:metabolism*; D013601:T-Lymphocytes / Q000276:immunology* / Q000378:metabolism*
chemical_list: D000954:Antigens, Surface; D015815:Cell Adhesion Molecules; D054415:Chemokine CCL19; D054421:Chemokine CCL21; C069886:L-selectin counter-receptors; C489082:Madcam1 protein, mouse; D008565:Membrane Proteins; D009088:Mucoproteins; D054400:Receptors, CCR7