title: Efficient cytokine-induced IL-13 production by mast cells requires both IL-33 and IL-3.
abstract: BACKGROUND
  IL-13 is a critical effector cytokine for allergic inflammation. It is produced by several cell types, including mast cells, basophils, and TH2 cells. In mast cells and basophils its induction can be stimulated by cross-linkage of immunoglobulin receptors or cytokines. The IL-1 family members IL-33 and IL-18 have been linked to induction of IL-13 production by mast cells and basophils. In CD4 TH2 cells IL-33-mediated production of IL-13 requires simultaneous signal transducer and activator of transcription (STAT) 5 activation.
  
  
  OBJECTIVE
  Here we have addressed whether cytokine-induced IL-13 production in mast cells and basophils follows the same logic as in TH2 cells: requirement of 2 separate signals.
  
  
  METHODS
  By generating a bacterial artificial chromosome (BAC) transgenic IL-13 reporter mouse, we measured IL-13 production in mast cells and basophils.
  
  
  RESULTS
  In mast cells harvested from peritoneal cavities, 2 cytokine signals are required for IL-13 production: IL-33 and IL-3. In bone marrow mast cells IL-13 production requires IL-33, but the requirement for a STAT5 inducer is difficult to evaluate because these cells require the continuous presence of IL-3 (a STAT5 activator) for survival. Poorer STAT5 inducers in culture (IL-4 or stem cell factor) result in less IL-13 production on IL-33 challenge, but the addition of exogenous IL-3 enhances IL-13 production. This implies that bone marrow-derived mast cells, like peritoneal mast cells and TH2 cells, require stimulation both by an IL-1 family member and a STAT5 inducer to secrete IL-13. Basophils follow the same rule; splenic basophils produce IL-13 in response to IL-18 or IL-33 plus IL-3.
  
  
  CONCLUSIONS
  Optimal IL-13 production from mast cells and basophils requires 2 cytokine signals.
authors.affiliation: Laboratory of Immunology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Md; School of Medicine, University of Tampere, Tampere, Finland; Fimlab Laboratories, Pirkanmaa Hospital District, Tampere, Finland. Electronic address: ilkka.junttila@uta.fi.
authors.forename: Ilkka S
authors.initials: IS
authors.lastname: Junttila
authors.affiliation: Laboratory of Immunology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Md.
authors.forename: Cynthia
authors.initials: C
authors.lastname: Watson
authors.affiliation: School of Medicine, University of Tampere, Tampere, Finland.
authors.forename: Laura
authors.initials: L
authors.lastname: Kummola
authors.affiliation: Laboratory of Immunology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Md.
authors.forename: Xi
authors.initials: X
authors.lastname: Chen
authors.affiliation: Laboratory of Immunology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Md.
authors.forename: Jane
authors.initials: J
authors.lastname: Hu-Li
authors.affiliation: Laboratory of Immunology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Md.
authors.forename: Liying
authors.initials: L
authors.lastname: Guo
authors.affiliation: Laboratory of Immunology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Md.
authors.forename: Ryoji
authors.initials: R
authors.lastname: Yagi
authors.affiliation: Laboratory of Immunology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Md. Electronic address: wpaul@niaid.nih.gov.
authors.forename: William E
authors.initials: WE
authors.lastname: Paul
mesh_terms: D000818:Animals; D001491:Basophils / Q000187:drug effects / Q000276:immunology*; D001854:Bone Marrow Cells / Q000166:cytology; D002478:Cells, Cultured; D016207:Cytokines / Q000276:immunology* / Q000494:pharmacology; D000072179:Interleukin-1 Receptor-Like 1 Protein; D008407:Mast Cells / Q000187:drug effects / Q000276:immunology*; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D018123:Receptors, Interleukin / Q000276:immunology; D053724:Receptors, Interleukin-18 / Q000276:immunology; D050799:STAT5 Transcription Factor / Q000276:immunology
chemical_list: D016207:Cytokines; C486189:Il1rl1 protein, mouse; D000072179:Interleukin-1 Receptor-Like 1 Protein; D018123:Receptors, Interleukin; D053724:Receptors, Interleukin-18; D050799:STAT5 Transcription Factor
keywords: BAC; BAC transgenic mouse; BMMC; Bacterial artificial chromosome; Bone marrow–derived mast cell; DsRed fluorochrome; IL-18 receptor; IL-18R; Mast cells; SCF; STAT; Signal transducer and activator of transcription; Stem cell factor; WT; Wild-type; allergic inflammation; basophils; cytokines; signal transducer and activator of transcription 5; tyrosine phosphorylation