title: Thymic stromal lymphopoietin and IL-33 modulate migration of hematopoietic progenitor cells in patients with allergic asthma.
abstract: BACKGROUND
  Thymic stromal lymphopoietin (TSLP) and IL-33 are considered important initiators of type 2 immunity. In asthmatic patients allergic inflammatory responses are associated with increased lung homing of bone marrow-derived CD34(+) hematopoietic progenitor cells (HPCs), which include eosinophil lineage-committed progenitor cells. In this study we investigated the role of TSLP and IL-33 in the recruitment of progenitor cells to the airways in asthmatic subjects.
  
  
  OBJECTIVE
  We sought (i) to examine the effect of allergen inhalation challenge on expression levels of receptors for TSLP (thymic stromal lymphopoietin receptor [TSLPR] and CD127) and IL-33 (ST2) and (ii) investigate the functional effects of these cytokines on HPCs.
  
  
  METHODS
  Consenting patients with mild atopic asthma (n = 19) with an FEV1 of 70% or greater and methacholine PC20 of 16 mg/mL or less were recruited. Blood- and sputum-extracted progenitors were phenotyped by flow cytometry before and 24 hours after allergen challenge. Functional responses, including cytokine production and migration to TSLP and IL-33, were assessed in vitro.
  
  
  RESULTS
  Significant increases in mature eosinophil, HPC, and eosinophil lineage-committed progenitor cell counts in sputum were observed 24 hours after allergen and were associated with a significant allergen-induced increase in HPCs expressing TSLPR, CD127, and ST2. Pre-exposure to TSLP and IL-33 primed the migration of HPCs to a potent progenitor cell chemoattractant, stromal cell-derived factor 1α (CXCL12). Incubation with TSLP and IL-33 stimulated significant production of IL-5 and IL-13, but not IL-4, by HPCs. This priming effect was inhibited by blocking antibodies to TSLPR and ST2, respectively, and IL-13 receptor α1 in both scenarios.
  
  
  CONCLUSIONS
  In allergic asthmatic responses increased lung homing of HPCs may be orchestrated by TSLP and IL-33 through an IL-13-dependent axis.
authors: Firestone Institute for Respiratory Health, St Joseph's Healthcare, Hamilton, Ontario, Canada.
authors: Steven G
authors: SG
authors: Smith
authors: Firestone Institute for Respiratory Health, St Joseph's Healthcare, Hamilton, Ontario, Canada.
authors: Akash
authors: A
authors: Gugilla
authors: Firestone Institute for Respiratory Health, St Joseph's Healthcare, Hamilton, Ontario, Canada.
authors: Manali
authors: M
authors: Mukherjee
authors: Firestone Institute for Respiratory Health, St Joseph's Healthcare, Hamilton, Ontario, Canada.
authors: Kayla
authors: K
authors: Merim
authors: Firestone Institute for Respiratory Health, St Joseph's Healthcare, Hamilton, Ontario, Canada.
authors: Anam
authors: A
authors: Irshad
authors: Asthma Research Group, Department of Medicine, McMaster University, Hamilton, Ontario, Canada.
authors: Wei
authors: W
authors: Tang
authors: Asthma Research Group, Department of Medicine, McMaster University, Hamilton, Ontario, Canada.
authors: Takashi
authors: T
authors: Kinoshita
authors: Asthma Research Group, Department of Medicine, McMaster University, Hamilton, Ontario, Canada.
authors: Brittany
authors: B
authors: Watson
authors: Asthma Research Group, Department of Medicine, McMaster University, Hamilton, Ontario, Canada.
authors: John-Paul
authors: JP
authors: Oliveria
authors: Inflammation Research, Amgen, Seattle, Wash.
authors: Mike
authors: M
authors: Comeau
authors: Asthma Research Group, Department of Medicine, McMaster University, Hamilton, Ontario, Canada.
authors: Paul M
authors: PM
authors: O'Byrne
authors: Asthma Research Group, Department of Medicine, McMaster University, Hamilton, Ontario, Canada.
authors: Gail M
authors: GM
authors: Gauvreau
authors: Firestone Institute for Respiratory Health, St Joseph's Healthcare, Hamilton, Ontario, Canada. Electronic address: sehmir@mcmaster.ca.
authors: Roma
authors: R
authors: Sehmi
mesh_terms: D000280:Administration, Inhalation; D000328:Adult; D000485:Allergens / Q000494:pharmacology; D001249:Asthma / Q000235:genetics / Q000276:immunology* / Q000473:pathology; D002465:Cell Movement / Q000187:drug effects; D054377:Chemokine CXCL12 / Q000235:genetics / Q000276:immunology; D016207:Cytokines / Q000235:genetics / Q000276:immunology*; D004804:Eosinophils / Q000187:drug effects / Q000276:immunology* / Q000473:pathology; D005541:Forced Expiratory Volume; D005786:Gene Expression Regulation; D006412:Hematopoietic Stem Cells / Q000187:drug effects / Q000276:immunology* / Q000473:pathology; D006801:Humans; D007113:Immunity, Innate; D000072179:Interleukin-1 Receptor-Like 1 Protein; D018793:Interleukin-13 / Q000235:genetics / Q000276:immunology; D053661:Interleukin-13 Receptor alpha1 Subunit / Q000235:genetics / Q000276:immunology; D000067596:Interleukin-33; D015848:Interleukin-5 / Q000235:genetics / Q000276:immunology; D053699:Interleukin-7 Receptor alpha Subunit / Q000235:genetics / Q000276:immunology; D007378:Interleukins / Q000235:genetics / Q000276:immunology*; D008297:Male; D016210:Methacholine Chloride / Q000494:pharmacology; D008875:Middle Aged; D061251:Primary Cell Culture; D011956:Receptors, Cell Surface / Q000235:genetics / Q000276:immunology; D018121:Receptors, Cytokine / Q000235:genetics / Q000276:immunology; D013183:Sputum / Q000166:cytology / Q000276:immunology; D000094632:Thymic Stromal Lymphopoietin
chemical_list: D000485:Allergens; C498762:CRLF2 protein, human; C515255:CXCL12 protein, human; D054377:Chemokine CXCL12; D016207:Cytokines; C578095:IL13 protein, human; C079241:IL1RL1 protein, human; C506536:IL33 protein, human; C508599:IL5 protein, human; D000072179:Interleukin-1 Receptor-Like 1 Protein; D018793:Interleukin-13; D053661:Interleukin-13 Receptor alpha1 Subunit; D000067596:Interleukin-33; D015848:Interleukin-5; D053699:Interleukin-7 Receptor alpha Subunit; D007378:Interleukins; D011956:Receptors, Cell Surface; D018121:Receptors, Cytokine; D016210:Methacholine Chloride; D000094632:Thymic Stromal Lymphopoietin
keywords: Hematopoietic progenitor cells; asthma; thymic stromal lymphopoietin