title: CCL2/CCR2-dependent recruitment of Th17 cells but not Tc17 cells to the lung in a murine asthma model.
abstract: BACKGROUND
  Interleukin (IL)-17 has been implicated in the pathogenesis of asthma and the progression of airway inflammation. Here, we used a model of allergic asthma and found that the frequencies of IL-17-secreting T helper (Th)17 and CD8 (Tc)17 cells were both significantly increased, as was the expression of the CC chemokine receptor (CCR2) on the surface of these cells. CC chemokine ligand 2 (CCL2) has been shown to mediate the activation and recruitment of inflammatory cells in asthma, which are also skewed after ovalbumin (OVA) challenge. However, the role of CCL2 on Th17 cells and Tc17 cells in asthma has not been illuminated.
  
  
  METHODS
  Mice that were sensitized and challenged with OVA received anti-CCL2 antibody (Ab; 5 μg/day intratracheally) or CCR2 antagonist (RS504393, 2 mg/kg/day intraperitoneally) prior to the challenge. Some mice received an isotype control Ab or vehicle alone. We then assessed the effects of allergic asthma and anti-CCL2 Ab or CCR2 antagonist treatment on the levels of IL-17 and CCL2, the Th17 and Tc17 cell frequencies and lung tissue inflammation.
  
  
  RESULTS
  We demonstrated that CCL2 and IL-17 levels and the frequency of Th17 and Tc17 cells in lung tissues and bronchoalveolar lavage fluid increased in the asthma group compared with the normal control mice. Blocking the CCL2/CCR2 axis greatly reduced the Th17 but not the Tc17 cell frequency, and revealed a suppressive effect on airway inflammation.
  
  
  CONCLUSIONS
  These findings indicate a role for the CCL2/CCR2 axis in mediating Th17 but not Tc17 cell migration during acute allergic airway inflammation.
authors.affiliation: Department of Respiratory and Critical Care Medicine, Tongji Hospital and Key Laboratory of Pulmonary Diseases of Health Ministry, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, PR China.
authors.forename: Aili
authors.initials: A
authors.lastname: Wang
authors.forename: Zhengyun
authors.initials: Z
authors.lastname: Wang
authors.forename: Yong
authors.initials: Y
authors.lastname: Cao
authors.forename: Sheng
authors.initials: S
authors.lastname: Cheng
authors.forename: Huilong
authors.initials: H
authors.lastname: Chen
authors.forename: Hansvin
authors.initials: H
authors.lastname: Bunjhoo
authors.forename: Jungang
authors.initials: J
authors.lastname: Xie
authors.forename: Congyi
authors.initials: C
authors.lastname: Wang
authors.forename: Yongjian
authors.initials: Y
authors.lastname: Xu
authors.forename: Weining
authors.initials: W
authors.lastname: Xiong
mesh_terms: D000818:Animals; D057134:Antibodies, Neutralizing / Q000494:pharmacology; D001249:Asthma / Q000139:chemically induced / Q000235:genetics / Q000276:immunology* / Q000473:pathology; D048588:Benzoxazines / Q000494:pharmacology; D001992:Bronchoalveolar Lavage Fluid / Q000737:chemistry / Q000166:cytology / Q000276:immunology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology* / Q000473:pathology; D018932:Chemokine CCL2 / Q000037:antagonists & inhibitors / Q000235:genetics / Q000276:immunology*; D004195:Disease Models, Animal; D005260:Female; D015870:Gene Expression; D006801:Humans; D020381:Interleukin-17 / Q000096:biosynthesis / Q000276:immunology; D008168:Lung / Q000276:immunology* / Q000473:pathology; D018655:Lymphocyte Count; D051379:Mice; D008807:Mice, Inbred BALB C; D010047:Ovalbumin; D054390:Receptors, CCR2 / Q000037:antagonists & inhibitors / Q000235:genetics / Q000276:immunology*; D013141:Spiro Compounds / Q000494:pharmacology; D058504:Th17 Cells / Q000276:immunology* / Q000473:pathology
chemical_list: D057134:Antibodies, Neutralizing; D048588:Benzoxazines; C491768:Ccl2 protein, mouse; C515335:Ccr2 protein, mouse; D018932:Chemokine CCL2; D020381:Interleukin-17; C579117:RS 504393; D054390:Receptors, CCR2; D013141:Spiro Compounds; D010047:Ovalbumin