title: Repeated FcεRI triggering reveals modified mast cell function related to chronic allergic responses in tissue.
abstract: Activation of mast cells through FcεRI plays an important role in acute allergic reactions. However, little is known about the function of mast cells in patients with chronic allergic inflammation or the effect of repeated FcεRI triggering occurring in such responses.
  
  
  
  We aimed to identify changes in mast cell function after repeated FcεRI triggering and to correlate these changes to chronic allergic responses in tissue.
  
  
  
  Human cord blood-derived mast cells were treated for 2 weeks with anti-IgE. The function of naive or treated mast cells was analyzed by means of RNA sequencing, quantitative RT-PCR, flow cytometry, and functional assays. Protein secretion was measured with ELISAs and multiplex assays.
  
  
  
  We observed several changes in mast cell function after repeated anti-IgE triggering. Although the acute response was dampened, we identified 289 genes significantly upregulated after repeated anti-IgE. Most of these genes (84%) were not upregulated after a single anti-IgE stimulus, indicating a significantly different response mode characterized by increased antigen presentation, response to bacteria, and chemotaxis. Changes in mast cell function were related to changes in expression of the transcription factors RXRA and BATF and others. Importantly, we found a substantial overlap between genes upregulated after repeated anti-IgE triggering and genes upregulated in tissue from patients with chronic allergy, in particular those of patients with chronic rhinosinusitis.
  
  
  
  Our study provides evidence for intrinsic modulation of mast cell function on repeated FcεRI-mediated activation. The overlap with gene expression in tissues is suggestive of a direct link between repeated IgE-mediated activation of mast cells and chronic allergy.
authors.affiliation: Department of Rheumatology, Leiden University Medical Center, Leiden, The Netherlands.
authors.forename: Jolien
authors.initials: J
authors.lastname: Suurmond
authors.affiliation: Department of Rheumatology, Leiden University Medical Center, Leiden, The Netherlands.
authors.forename: Kim L L
authors.initials: KLL
authors.lastname: Habets
authors.affiliation: Department of Rheumatology, Leiden University Medical Center, Leiden, The Netherlands; Department of Human Genetics, Leiden University Medical Center, Leiden, The Netherlands.
authors.forename: Zuotian
authors.initials: Z
authors.lastname: Tatum
authors.affiliation: Department of Rheumatology, Leiden University Medical Center, Leiden, The Netherlands.
authors.forename: Joris J
authors.initials: JJ
authors.lastname: Schonkeren
authors.affiliation: Department of Human Genetics, Leiden University Medical Center, Leiden, The Netherlands.
authors.forename: Peter A C 't
authors.initials: PAC'
authors.lastname: Hoen
authors.affiliation: Department of Rheumatology, Leiden University Medical Center, Leiden, The Netherlands.
authors.forename: Tom W J
authors.initials: TWJ
authors.lastname: Huizinga
authors.affiliation: Department of Human Genetics, Leiden University Medical Center, Leiden, The Netherlands.
authors.forename: Jeroen F J
authors.initials: JFJ
authors.lastname: Laros
authors.affiliation: Department of Rheumatology, Leiden University Medical Center, Leiden, The Netherlands.
authors.forename: René E M
authors.initials: REM
authors.lastname: Toes
authors.affiliation: Department of Rheumatology, Leiden University Medical Center, Leiden, The Netherlands. Electronic address: b.a.s.kurreeman@lumc.nl.
authors.forename: Fina
authors.initials: F
authors.lastname: Kurreeman
mesh_terms: D000888:Antibodies, Anti-Idiotypic / Q000494:pharmacology; D002908:Chronic Disease; D015870:Gene Expression; D006801:Humans; D006967:Hypersensitivity / Q000235:genetics / Q000276:immunology*; D007073:Immunoglobulin E / Q000276:immunology; D008407:Mast Cells / Q000187:drug effects / Q000276:immunology*; D017455:Receptors, IgE / Q000276:immunology*; D014157:Transcription Factors / Q000235:genetics
chemical_list: D000888:Antibodies, Anti-Idiotypic; D017455:Receptors, IgE; D014157:Transcription Factors; C026408:anti-IgE antibodies; D007073:Immunoglobulin E
keywords: IgE; Mast cells; atopic asthma; atopic dermatitis; chronic allergy; chronic rhinosinusitis; transcriptome