Absence of CCR8 does not impair the response to ovalbumin-induced allergic airway disease.
Interaction of chemokines with their specific receptors results in tight control of leukocyte migration and positioning. CCR8 is a chemokine receptor expressed mainly in CD4(+) single-positive thymocytes and Th2 cells. We generated CCR8-deficient mice (CCR8(-/-)) to study the in vivo role of this receptor, and describe in this study the CCR8(-/-) mouse response in OVA-induced allergic airway disease using several models, including an adoptive transfer model and receptor-blocking experiments. All CCR8(-/-) mice developed a pathological response similar to that of wild-type animals with respect to bronchoalveolar lavage cell composition, peripheral blood and bone marrow eosinophilia, lung infiltrates, and Th2 cytokine levels in lung and serum. The results contrast with a recent report using one of the OVA-induced asthma models studied here. Similar immune responses were also observed in CCR8(-/-) and wild-type animals in a different model of ragweed allergen-induced peritoneal eosinophilic inflammation, with an equivalent number of eosinophils and analogous increased levels of Th2 cytokines in peritoneum and peripheral blood. Our results show that allergic diseases course without critical CCR8 participation, and suggest that further work is needed to unravel the in vivo role of CCR8 in Th2-mediated pathologies.
Goya
Iñigo
I
Departamento de Inmunología y Oncología, Centro Nacional de Biotecnología/Consejo Superior de Investigaciones Cientificas, Universidad Autónoma de Madrid, Cantoblanco, 28040-Madrid, Spain.
Villares
Ricardo
R
Zaballos
Angel
A
Gutiérrez
Julio
J
Kremer
Leonor
L
Gonzalo
José-Angel
JA
Varona
Rosa
R
Carramolino
Laura
L
Serrano
Alfredo
A
Pallarés
Pilar
P
Criado
Luis Miguel
LM
Kolbeck
Roland
R
Torres
Miguel
M
Coyle
Anthony J
AJ
Gutiérrez-Ramos
José-Carlos
JC
Martínez-A
Carlos
C
Márquez
Gabriel
G
D019264:Adoptive Transfer; D000485:Allergens / Q000008:administration & dosage / Q000276:immunology*; D000818:Animals; D000911:Antibodies, Monoclonal / Q000494:pharmacology; D019742:Chemokines, CC / Q000378:metabolism*; D003433:Crosses, Genetic; D004195:Disease Models, Animal; D004802:Eosinophilia / Q000276:immunology / Q000473:pathology; D005260:Female; D007274:Injections, Intraperitoneal; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D010047:Ovalbumin / Q000008:administration & dosage / Q000276:immunology*; D010538:Peritonitis / Q000276:immunology / Q000473:pathology; D054401:Receptors, CCR8; D019707:Receptors, Chemokine / Q000037:antagonists & inhibitors / Q000172:deficiency* / Q000235:genetics* / Q000276:immunology; D011995:Recombination, Genetic / Q000276:immunology; D012130:Respiratory Hypersensitivity / Q000235:genetics* / Q000276:immunology* / Q000473:pathology; D018418:Th2 Cells / Q000276:immunology / Q000378:metabolism; D013997:Time Factors
D000485:Allergens; D000911:Antibodies, Monoclonal; C103330:CCR8 protein, human; D019742:Chemokines, CC; D054401:Receptors, CCR8; D019707:Receptors, Chemokine; D010047:Ovalbumin