CCR8 is not essential for the development of inflammation in a mouse model of allergic airway disease.
Chemokine receptors play an important role in the trafficking of various immune cell types to sites of inflammation. Several chemokine receptors are differentially expressed in Th1 and Th2 effector populations. Th2 cells selectively express CCR3, CCR4, and CCR8, which could direct their trafficking to sites of allergic inflammation. Additionally, increased expression of the CCR8 ligand, TCA-3, has been detected in affected lungs in a mouse model of asthma. In this study, CCR8-deficient mice were generated to address the biological role of CCR8 in a model of allergic airway disease. Using two different protocols of allergen challenge, we demonstrate that absence of CCR8 does not affect the development of pulmonary eosinophilia and Th2 cytokine responses. In addition, administration of anti-TCA-3-neutralizing Ab during allergen sensitization and rechallenge failed to inhibit airway allergic inflammation. These results suggest that CCR8 does not play an essential role in the pathogenesis of inflammation in this mouse model of allergic airway disease.
Chung
Chan D
CD
Tularik, Inc., South San Francisco, CA 94080, USA.
Kuo
Frederick
F
Kumer
Jeffrey
J
Motani
Alykhan S
AS
Lawrence
Christopher E
CE
Henderson
William R
WR
Venkataraman
Chandrasekar
C
D000818:Animals; D019138:Antibodies, Blocking / Q000008:administration & dosage; D000941:Antigens / Q000008:administration & dosage / Q000276:immunology; D001992:Bronchoalveolar Lavage Fluid / Q000737:chemistry / Q000276:immunology; D002464:Cell Migration Inhibition; D054402:Chemokine CCL1; D019742:Chemokines, CC / Q000378:metabolism*; D003433:Crosses, Genetic; D016207:Cytokines / Q000037:antagonists & inhibitors / Q000276:immunology; D004195:Disease Models, Animal; D004306:Dose-Response Relationship, Immunologic; D004334:Drug Administration Schedule; D005260:Female; D007249:Inflammation / Q000235:genetics / Q000276:immunology / Q000473:pathology; D007274:Injections, Intraperitoneal; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D010047:Ovalbumin / Q000008:administration & dosage / Q000276:immunology; D054401:Receptors, CCR8; D019707:Receptors, Chemokine / Q000096:biosynthesis / Q000172:deficiency / Q000235:genetics / Q000502:physiology*; D012130:Respiratory Hypersensitivity / Q000235:genetics / Q000276:immunology* / Q000473:pathology*
D019138:Antibodies, Blocking; D000941:Antigens; C065971:CCL1 protein, human; C103330:CCR8 protein, human; C489319:Ccr8 protein, mouse; D054402:Chemokine CCL1; D019742:Chemokines, CC; D016207:Cytokines; D054401:Receptors, CCR8; D019707:Receptors, Chemokine; D010047:Ovalbumin