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Leukocyte attraction through the CCR5 receptor controls progress from insulitis to diabetes in non‐obese diabetic mice
Author(s) -
CarvalhoPinto Carla,
García María I.,
Gómez Lucio,
Ballesteros André,
Zaballos Angel,
Flores Juana M.,
Mellado Mario,
RodríguezFrade José Miguel,
Balomenos Dimitrios,
MartínezA. Carlos
Publication year - 2004
Publication title -
european journal of immunology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.272
H-Index - 201
eISSN - 1521-4141
pISSN - 0014-2980
DOI - 10.1002/eji.200324285
Subject(s) - insulitis , biology , nod mice , pancreatic islets , chemokine , islet , nod , chemokine receptor ccr5 , immunology , chemokine receptor , ccl5 , receptor , diabetes mellitus , endocrinology , medicine , t cell , inflammation , immune system , il 2 receptor , biochemistry
Abstract Lymphocyte infiltration to pancreatic islets is associated to chemoattraction, as are other inflammatory autoimmune processes. We examined whether development of insulitis and diabetes dependson 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 β‐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.