title: Selective deregulation in chemokine signaling pathways of CD4+CD25(hi)CD127(lo)/(-) regulatory T cells in human allergic asthma.
abstract: BACKGROUND
  CD4+CD25(hi)CD127(lo)/(-) regulatory T cells have been suggested to be critical regulators of inflammatory processes in allergic asthma. Recent studies reported a selective decrease in the frequency of regulatory T cells in the bronchoalveolar lavage fluid of allergic asthmatic (AA) subjects, prompting the possibility of defective recruitment of these cells to the airway in response to chemokines produced during asthmatic inflammation.
  
  
  OBJECTIVE
  This study aimed to characterize the chemotactic profile of circulating regulatory T cells in AA subjects in response to chemokines abundantly produced in airway inflammation, such as CCL1, CCL17, and CCL22.
  
  
  METHODS
  The study was performed in a cohort of 26 AA, 16 healthy control, and 16 non-AA subjects. We used chemotaxis assays to evaluate cell migration, flow cytometry to examine chemokine receptor expression, and phospho-ELISA to study consequent signaling pathways in regulatory T cells.
  
  
  RESULTS
  Regulatory T cells, but not CD4+CD25(-)T cells, from AA subjects showed decreased chemotactic responses, specifically to CCL1, in comparison with their healthy control and non-AA counterparts. Decreased CCL1-mediated chemotaxis in AA regulatory T cells was associated with decreased phosphorylation of protein kinase B (AKT), a protein involved in chemokine intracellular signaling. Furthermore, the decreased chemotactic response to CCL1 in AA regulatory T cells significantly correlated with asthma severity and decreased pulmonary function in AA subjects.
  
  
  CONCLUSIONS
  These results provide the first evidence of dysfunction in the chemokine signaling pathway in AA regulatory T cells.
authors.affiliation: Department of Pediatrics, Stanford University, Stanford, CA 94305, USA.
authors.forename: Khoa D
authors.initials: KD
authors.lastname: Nguyen
authors.forename: Christopher
authors.initials: C
authors.lastname: Vanichsarn
authors.forename: Alison
authors.initials: A
authors.lastname: Fohner
authors.forename: Kari C
authors.initials: KC
authors.lastname: Nadeau
mesh_terms: D000305:Adrenal Cortex Hormones / Q000494:pharmacology; D001249:Asthma / Q000276:immunology* / Q000503:physiopathology; D054402:Chemokine CCL1 / Q000502:physiology; D018925:Chemokines / Q000502:physiology*; D002633:Chemotaxis; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism; D005541:Forced Expiratory Volume; D006801:Humans; D053699:Interleukin-7 Receptor alpha Subunit / Q000032:analysis*; D010766:Phosphorylation; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D054398:Receptors, CCR4 / Q000032:analysis; D054401:Receptors, CCR8 / Q000032:analysis; D015398:Signal Transduction / Q000502:physiology*; D050378:T-Lymphocytes, Regulatory / Q000502:physiology*
chemical_list: D000305:Adrenal Cortex Hormones; C065971:CCL1 protein, human; C515354:CCR4 protein, human; C103330:CCR8 protein, human; D054402:Chemokine CCL1; D018925:Chemokines; D053699:Interleukin-7 Receptor alpha Subunit; D054398:Receptors, CCR4; D054401:Receptors, CCR8; D051057:Proto-Oncogene Proteins c-akt; D048049:Extracellular Signal-Regulated MAP Kinases