Leukocyte attraction through the CCR5 receptor controls progress from insulitis to diabetes in non-obese diabetic mice.
Lymphocyte infiltration to pancreatic islets is associated to chemoattraction, as are other inflammatory autoimmune processes. We examined whether development of insulitis and diabetes depends on chemoattraction of lymphocytes via the CCR5 chemokine receptor. In non-obese diabetic (NOD) mice, a substantial fraction of peripheral T cells and virtually all B cells expressed high CCR5 levels. CCR5 expression characterized the effector T cell phenotype, suggesting their potential involvement in disease development. In view of these findings and the CCL5 (RANTES, the CCR5 ligand) expression by pancreatic islets, we treated NOD mice with a neutralizing anti-CCR5 antibody. This did not influence peri-insulitis advancement, but inhibited beta-cell destruction and diabetes. These data demonstrate a role of CCR5-dependent chemoattraction in insulitis progression to islet destruction, suggesting the potential value of therapeutic intervention by CCR5 targeting.
Carvalho-Pinto
Carla
C
Department of Immunology and Oncology, Centro Nacional de Biotecnología/CSIC, UAM Campus de Cantoblanco, Madrid, Spain.
García
María I
MI
Gómez
Lucio
L
Ballesteros
André
A
Zaballos
Angel
A
Flores
Juana M
JM
Mellado
Mario
M
Rodríguez-Frade
José Miguel
JM
Balomenos
Dimitrios
D
Martínez-A
Carlos
C
D000818:Animals; D001402:B-Lymphocytes / Q000276:immunology*; D002465:Cell Movement / Q000276:immunology; D018925:Chemokines / Q000235:genetics / Q000276:immunology; D003920:Diabetes Mellitus / Q000276:immunology*; D005260:Female; D005434:Flow Cytometry; D007150:Immunohistochemistry; D007515:Islets of Langerhans / Q000276:immunology / Q000473:pathology; D008213:Lymphocyte Activation / Q000276:immunology; D051379:Mice; D016688:Mice, Inbred NOD; D012313:RNA / Q000235:genetics / Q000276:immunology; D019713:Receptors, CCR5 / Q000276:immunology*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013601:T-Lymphocytes / Q000276:immunology*
D018925:Chemokines; D019713:Receptors, CCR5; D012313:RNA