title: Elevated levels of circulating CD4(+) CRTh2(+) T cells characterize severe asthma.
abstract: Chemoattractant receptor-homologous molecule expressed on Th2 cells (CRTh2) is a receptor for PGD2 and expressed by T cells, eosinophils, basophils, and ILC2 cells. CRTh2 expression by CD4(+) T cells identifies the Th2 subset, and these cells have been characterized as allergen-specific central memory Th2 cells. Recently, activation of the PGD2 -CRTh2 pathway in the lungs was associated with severe asthma.
  
  
  
  To assess circulating levels of Th2 cells and related mediators in severe asthma and those who experience asthma exacerbations.
  
  
  
  Peripheral blood cells expressing CRTh2 were characterized by flow cytometry and qRT-PCR. Serum IL-13 and PGD2 were measured by ELISA and compared with asthma severity and tendency to exacerbate.
  
  
  
  Severe asthmatics had more circulating CD4(+) CRTh2(+) T cells, CRTh2 and GATA3 mRNA, and a higher level of serum IL-13 compared to mild/moderate asthmatics. The proportion of CD4(+) CRTh2(+) T cells was associated with lower lung function and was highest in severe asthmatics that exacerbated in the last year. Circulating CD4(+) CRTh2(+) T cells, unlike eosinophils, were positively correlated with inhaled steroid dose.
  
  
  
  Elevated levels of circulating CD4(+) CRTh2(+) T cells are a feature of severe asthma, despite high-dose corticosteroids. Tracking the systemic level of these cells may help identify type 2 severe asthmatics at risk of exacerbation.
authors.affiliation: Pulmonary Research Group, Department of Medicine, University of Alberta, Edmonton, AB, Canada.
authors.forename: N S
authors.initials: NS
authors.lastname: Palikhe
authors.affiliation: Pulmonary Research Group, Department of Medicine, University of Alberta, Edmonton, AB, Canada.
authors.forename: C
authors.initials: C
authors.lastname: Laratta
authors.affiliation: Pulmonary Research Group, Department of Medicine, University of Alberta, Edmonton, AB, Canada.
authors.forename: D
authors.initials: D
authors.lastname: Nahirney
authors.affiliation: Pulmonary Research Group, Department of Medicine, University of Alberta, Edmonton, AB, Canada.
authors.forename: D
authors.initials: D
authors.lastname: Vethanayagam
authors.affiliation: Pulmonary Research Group, Department of Medicine, University of Alberta, Edmonton, AB, Canada.
authors.forename: M
authors.initials: M
authors.lastname: Bhutani
authors.affiliation: Pulmonary Research Group, Department of Medicine, University of Alberta, Edmonton, AB, Canada.
authors.forename: H
authors.initials: H
authors.lastname: Vliagoftis
authors.affiliation: Pulmonary Research Group, Department of Medicine, University of Alberta, Edmonton, AB, Canada.|Department of Pathology and Laboratory Medicine, Schulich School of Medicine & Dentistry, Western University, London, ON, Canada.
authors.forename: L
authors.initials: L
authors.lastname: Cameron
mesh_terms: D000305:Adrenal Cortex Hormones / Q000627:therapeutic use; D000328:Adult; D000818:Animals; D001249:Asthma / Q000097:blood* / Q000175:diagnosis / Q000276:immunology* / Q000378:metabolism; D015415:Biomarkers; D016207:Cytokines / Q000097:blood / Q000378:metabolism; D004195:Disease Models, Animal; D018450:Disease Progression; D020869:Gene Expression Profiling; D006801:Humans; D007073:Immunoglobulin E / Q000097:blood / Q000276:immunology; D016130:Immunophenotyping; D018836:Inflammation Mediators / Q000097:blood / Q000378:metabolism; D008213:Lymphocyte Activation / Q000276:immunology; D018655:Lymphocyte Count; D051379:Mice; D008875:Middle Aged; D010641:Phenotype; D012129:Respiratory Function Tests; D012307:Risk Factors; D012720:Severity of Illness Index; D015398:Signal Transduction; D016176:T-Lymphocyte Subsets / Q000276:immunology* / Q000378:metabolism; D018418:Th2 Cells / Q000276:immunology* / Q000378:metabolism
chemical_list: D000305:Adrenal Cortex Hormones; D015415:Biomarkers; D016207:Cytokines; D018836:Inflammation Mediators; D007073:Immunoglobulin E
keywords: CD4+CRTh2+ T cells; CRTh2; PGD
  2; Th2 cells; biomarker; exacerbation; glucocorticosteroid responsiveness; severe asthma; type 2 immunity