title: Attenuation of antigen-induced airway hyperresponsiveness and inflammation in CXCR3 knockout mice.
abstract: BACKGROUND
  CD8+ T cells participate in airway hyperresponsiveness (AHR) and allergic pulmonary inflammation that are characteristics of asthma. CXCL10 by binding to CXCR3 expressed preferentially on activated CD8+ T cells, attracts T cells homing to the lung. We studied the contribution and limitation of CXCR3 to AHR and airway inflammation induced by ovalbumin (OVA) using CXCR3 knockout (KO) mice.
  
  
  METHODS
  Mice were sensitized and challenged with OVA. Lung histopathological changes, AHR, cellular composition and levels of inflammatory mediators in bronchoalveolar lavage (BAL) fluid, and lungs at mRNA and protein levels, were compared between CXCR3 KO mice and wild type (WT) mice.
  
  
  RESULTS
  Compared with the WT controls, CXCR3 KO mice showed less OVA-induced infiltration of inflammatory cells around airways and vessels, and less mucus production. CXCR3 KO mice failed to develop significant AHR. They also demonstrated significantly fewer CD8+ T and CD4+ T cells in BAL fluid, lower levels of TNFα and IL-4 in lung tissue measured by real-time RT-PCR and in BAL fluid by ELISA, with significant elevation of IFNγ mRNA and protein expression levels.
  
  
  CONCLUSIONS
  We conclude that CXCR3 is crucial for AHR and airway inflammation by promoting recruitment of more CD8+ T cells, as well as CD4+ T cells, and initiating release of proinflammatory mediators following OVA sensitization and challenge. CXCR3 may represent a novel therapeutic target for asthma.
authors.affiliation: Department of Respiratory Diseases, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing 100730, China.
authors.forename: Yi
authors.initials: Y
authors.lastname: Lin
authors.forename: Haibo
authors.initials: H
authors.lastname: Yan
authors.forename: Yu
authors.initials: Y
authors.lastname: Xiao
authors.forename: Hongmei
authors.initials: H
authors.lastname: Piao
authors.forename: Ruolan
authors.initials: R
authors.lastname: Xiang
authors.forename: Lei
authors.initials: L
authors.lastname: Jiang
authors.forename: Huaxia
authors.initials: H
authors.lastname: Chen
authors.forename: Kewu
authors.initials: K
authors.lastname: Huang
authors.forename: Zijian
authors.initials: Z
authors.lastname: Guo
authors.forename: Wexun
authors.initials: W
authors.lastname: Zhou
authors.forename: Bao
authors.initials: B
authors.lastname: Lu
authors.forename: Jinming
authors.initials: J
authors.lastname: Gao
mesh_terms: D000818:Animals; D000941:Antigens / Q000008:administration & dosage* / Q000276:immunology; D016535:Bronchial Hyperreactivity / Q000276:immunology* / Q000473:pathology* / Q000517:prevention & control; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology / Q000473:pathology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology / Q000473:pathology; D005260:Female; D018836:Inflammation Mediators / Q000008:administration & dosage* / Q000276:immunology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D010047:Ovalbumin / Q000008:administration & dosage / Q000276:immunology; D054367:Receptors, CXCR3 / Q000172:deficiency* / Q000235:genetics*
chemical_list: D000941:Antigens; C515188:Cxcr3 protein, mouse; D018836:Inflammation Mediators; D054367:Receptors, CXCR3; D010047:Ovalbumin