title: IL-17A induces CCL28, supporting the chemotaxis of IgE-secreting B cells.
abstract: BACKGROUND
  Atopic asthma is an allergic disease typically associated with T(H)2 cytokines. IL-17A is also associated with asthma, through the induction of chemokines. Mucosal CCL28 concentrations correlate with cellular recruitment to inflamed airways and support migration of IgA(+) B cells. Here, a link between IL-17A, CCL28 and IgE-secreting B cell chemotaxis is examined.
  
  
  METHODS
  Primary human airway cells and the airway epithelial line A549 were used to characterize IL-17A receptor expression and the effect of IL-17A on CCL28 transcription and translation. B cells, differentiated to IgE+ cells ex vivo, were assessed for CCR10 surface expression and chemotaxis to CCL28 by flow cytometry, transwell migration and ELISpot.
  
  
  RESULTS
  Human airway epithelium expressed both IL-17RA and IL-17RC, and was responsive to IL-17A stimulation. Cultured human IgE+ B cells expressed surface CCR10 and displayed CCR10-dependent chemotaxis towards recombinant CCL28. Enhanced levels of CCL28 were observed upon A549 cell incubation with IL-17A, and this up-regulation significantly increased the migration of IgE+ antibody-secreting B cells. The specificity of chemotaxis was confirmed by migration blockade in the presence of anti-CCL28 or anti-CCR10.
  
  
  CONCLUSIONS
  This work identifies a novel chemokine for the migration of IgE+ B cells, in addition to characterizing induction of CCL28 by IL-17A. Taken together the results presented here propose a new role for IL-17A in the allergic airways, linking this cytokine with the recruitment of IgE+ antibody-secreting B cells, via the induction of CCL28. These observations justify further in vivo studies of larger cohorts.
authors: Cellular Immunology Laboratory, Institute of Immunology, National University of Ireland Maynooth, Maynooth, Ireland.
authors: Karen M
authors: KM
authors: Scanlon
authors: Richard J
authors: RJ
authors: Hawksworth
authors: Stephen J
authors: SJ
authors: Lane
authors: Bernard P
authors: BP
authors: Mahon
mesh_terms: D000293:Adolescent; D001249:Asthma / Q000276:immunology / Q000378:metabolism; D001402:B-Lymphocytes / Q000276:immunology / Q000378:metabolism / Q000502:physiology*; D002460:Cell Line; D002478:Cells, Cultured; D019742:Chemokines, CC / Q000235:genetics / Q000378:metabolism*; D002634:Chemotaxis, Leukocyte / Q000502:physiology*; D006801:Humans; D006967:Hypersensitivity / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D007073:Immunoglobulin E / Q000378:metabolism*; D020381:Interleukin-17 / Q000276:immunology* / Q000378:metabolism; D054447:Receptors, CCR10 / Q000096:biosynthesis / Q000235:genetics
chemical_list: C414047:CCL28 protein, human; D019742:Chemokines, CC; D020381:Interleukin-17; D054447:Receptors, CCR10; D007073:Immunoglobulin E