title: Human eosinophils release IL-1ß and increase expression of IL-17A in activated CD4+ T lymphocytes.
abstract: BACKGROUND
  Differentiation and activation of CD4(+) T cells is controlled by various cytokines produced by innate immune cells. We have shown that eosinophils (EOS) have the potential to influence Th1 and Th2 cytokine generation by CD4(+) cells, but their influence on IL-17A (IL-17) has not been established.
  
  
  OBJECTIVE
  The purpose of this study is to determine the effect of EOS on IL-17 production by lymphocytes.
  
  
  METHODS
  Pre-activated CD4(+) T cells were cultured in the presence of either autologous EOS or EOS culture supernatants. Expression of IL-17 was determined by real-time quantitative PCR (qPCR) after 5 h and protein level was measured after 48 h. To determine the effect of allergen-induced airway EOS on IL-17, subjects with mild allergic asthma underwent bronchoscopic segmental bronchoprovocation with allergen (SBP-Ag) after a treatment with an anti-IL-5 neutralizing antibody (mepolizumab) to reduce airway eosinophilia. IL-17 mRNA was measured in bronchoalveolar lavage (BAL) cells by qPCR.
  
  
  RESULTS
  In vitro, EOS significantly increased IL-17 production by CD4(+) T cells. Addition of exogenous IL-1ß increased expression of IL-17 mRNA by CD4(+) T cells. EOS expressed and released IL-1ß. Furthermore, levels of IL-1ß in EOS supernatants highly correlated with their ability to increase IL-17 expression by CD4(+) T cells, and neutralizing antibody to IL-1ß reduced expression of IL-17 mRNA. In vivo, reduction of EOS in the airway using mepolizumab was associated with diminished IL-17 expression after SBP-Ag.
  
  
  CONCLUSIONS
  Our data demonstrate that EOS can promote IL-17 production through the release of IL-1ß. Enhanced IL-17 cytokine production is another mechanism by which EOS may participate in pathogenesis of allergic airway inflammation in asthma.
authors.affiliation: Division of Allergy, Pulmonary and Critical Care Medicine, Department of Medicine, University of Wisconsin School of Medicine and Public Health, Madison, WI 53792, USA. sesnault@medicine.wisc.edu
authors.forename: S
authors.initials: S
authors.lastname: Esnault
authors.forename: E A B
authors.initials: EA
authors.lastname: Kelly
authors.forename: L M
authors.initials: LM
authors.lastname: Nettenstrom
authors.forename: E B
authors.initials: EB
authors.lastname: Cook
authors.forename: C M
authors.initials: CM
authors.lastname: Seroogy
authors.forename: N N
authors.initials: NN
authors.lastname: Jarjour
mesh_terms: D061067:Antibodies, Monoclonal, Humanized / Q000627:therapeutic use; D001249:Asthma / Q000276:immunology* / Q000628:therapy; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology* / Q000378:metabolism; D002478:Cells, Cultured; D016207:Cytokines / Q000235:genetics / Q000378:metabolism; D004804:Eosinophils / Q000276:immunology / Q000378:metabolism*; D005786:Gene Expression Regulation / Q000276:immunology; D006801:Humans; D006967:Hypersensitivity; D020381:Interleukin-17 / Q000235:genetics / Q000378:metabolism*; D053583:Interleukin-1beta / Q000235:genetics / Q000378:metabolism*; D008213:Lymphocyte Activation / Q000276:immunology*; D016896:Treatment Outcome; D015854:Up-Regulation
chemical_list: D061067:Antibodies, Monoclonal, Humanized; D016207:Cytokines; D020381:Interleukin-17; D053583:Interleukin-1beta; C434107:mepolizumab