Attenuation of antigen-induced airway hyperresponsiveness and inflammation in CXCR3 knockout mice

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• 作者：Yi Lin (1)
  Haibo Yan (2)
  Yu Xiao (3)
  Hongmei Piao (2)
  Ruolan Xiang (4)
  Lei Jiang (1)
  Huaxia Chen (1)
  Kewu Huang (5)
  Zijian Guo (1)
  Wexun Zhou (3)
  Bao Lu (6)
  Jinming Gao (1)
  
• 关键词：chemokine receptor ; CXCR3 ; CD8+ T lymphocyte ; airway inflammation ; airway hyperresponsiveness
• 刊名：Respiratory Research
• 出版年：2011
• 出版时间：December 2011
• 年：2011
• 卷：12
• 期：1
• 全文大小：353KB
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• 作者单位：Yi Lin (1)
  Haibo Yan (2)
  Yu Xiao (3)
  Hongmei Piao (2)
  Ruolan Xiang (4)
  Lei Jiang (1)
  Huaxia Chen (1)
  Kewu Huang (5)
  Zijian Guo (1)
  Wexun Zhou (3)
  Bao Lu (6)
  Jinming Gao (1)
  
  1. Department of Respiratory Diseases, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, 100730, China
  2. Department of Respiratory Diseases, Yanbian University Affiliated Hospital, Yanbian, Jilin, 133000, China
  3. Department of Pathology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, 100730, China
  4. Department of Physiology and Pathophysiology, Peking University Health Sciences Center, Beijing, 100088, China
  5. Department of Respiratory Medicine, Chaoyang Hospital, Capital University of Medical Sciences, Beijing, 100023, China
  6. Ina Sue Perlmutter Laboratory, Children’s Hospital, Harvard Medical School, Boston, MA, 02115, USA
  

文摘

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.