title: CD69 controls the pathogenesis of allergic airway inflammation.
abstract: Airway inflammation and airway hyperresponsiveness are central issues in the pathogenesis of asthma. CD69 is a membrane molecule transiently expressed on activated lymphocytes, and its selective expression in inflammatory infiltrates suggests that it plays a role in the pathogenesis of inflammatory diseases. In CD69-deficient mice, OVA-induced eosinophilic airway inflammation, mucus hyperproduction, and airway hyperresponsiveness were attenuated. Cell transfer of Ag-primed wild-type but not CD69-deficient CD4 T cells restored the induction of allergic inflammation in CD69-deficient mice, indicating a critical role of CD69 expressed on CD4 T cells. Th2 responses induced by CD69-deficient CD4 T cells in the lung were attenuated, and the migration of CD4 T cells into the asthmatic lung was severely compromised. The expression of VCAM-1 was also substantially altered, suggesting the involvement of VCAM-1 in the CD69-dependent migration of Th2 cells into the asthmatic lung. Interestingly, the administration of anti-CD69 Ab inhibited the induction of the OVA-induced airway inflammation and hyperresponsiveness. This inhibitory effect induced by the CD69 mAb was observed even after the airway challenge with OVA. These results indicate that CD69 plays a crucial role in the pathogenesis of allergen-induced eosinophilic airway inflammation and hyperresponsiveness and that CD69 could be a possible therapeutic target for asthmatic patients.
authors.affiliation: Department of Immunology, Graduate School of Medicine, Chiba University, Chiba, Japan.
authors.forename: Takako
authors.initials: T
authors.lastname: Miki-Hosokawa
authors.forename: Akihiro
authors.initials: A
authors.lastname: Hasegawa
authors.forename: Chiaki
authors.initials: C
authors.lastname: Iwamura
authors.forename: Kenta
authors.initials: K
authors.lastname: Shinoda
authors.forename: Soichi
authors.initials: S
authors.lastname: Tofukuji
authors.forename: Yukiko
authors.initials: Y
authors.lastname: Watanabe
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Hosokawa
authors.forename: Shinichiro
authors.initials: S
authors.lastname: Motohashi
authors.forename: Kahoko
authors.initials: K
authors.lastname: Hashimoto
authors.forename: Mutsunori
authors.initials: M
authors.lastname: Shirai
authors.forename: Masakatsu
authors.initials: M
authors.lastname: Yamashita
authors.forename: Toshinori
authors.initials: T
authors.lastname: Nakayama
mesh_terms: D000485:Allergens / Q000008:administration & dosage / Q000276:immunology; D000818:Animals; D000911:Antibodies, Monoclonal / Q000008:administration & dosage / Q000627:therapeutic use; D015703:Antigens, CD / Q000235:genetics / Q000276:immunology / Q000502:physiology*; D000945:Antigens, Differentiation, T-Lymphocyte / Q000235:genetics / Q000276:immunology / Q000502:physiology*; D001249:Asthma / Q000276:immunology / Q000473:pathology; D016535:Bronchial Hyperreactivity / Q000276:immunology / Q000473:pathology / Q000517:prevention & control; D004195:Disease Models, Animal; D004804:Eosinophils / Q000276:immunology / Q000473:pathology; D018836:Inflammation Mediators / Q000378:metabolism / Q000502:physiology*; D037181:Lectins, C-Type / Q000235:genetics / Q000276:immunology / Q000502:physiology*; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008822:Mice, Transgenic; D010047:Ovalbumin / Q000008:administration & dosage / Q000276:immunology; D012130:Respiratory Hypersensitivity / Q000276:immunology* / Q000473:pathology* / Q000517:prevention & control; D000099192:CD69 Antigens
chemical_list: D000485:Allergens; D000911:Antibodies, Monoclonal; D015703:Antigens, CD; D000945:Antigens, Differentiation, T-Lymphocyte; D018836:Inflammation Mediators; D037181:Lectins, C-Type; D010047:Ovalbumin; D000099192:CD69 Antigens