Efficient cytokine-induced IL-13 production by mast cells requires both IL-33 and IL-3

• Published in: Journal of allergy and clinical immunology Vol. 132; no. 3; pp. 704 - 712.e10
• Main Authors: Junttila, Ilkka S., MD, PhD, Watson, Cynthia, BSc, Kummola, Laura, MSc, Chen, Xi, MD, Hu-Li, Jane, BSc, Guo, Liying, PhD, Yagi, Ryoji, PhD, Paul, William E., MD
• Format: Journal Article
• Language: English
• Published: New York, NY Elsevier Inc 01.09.2013; Elsevier; Elsevier Limited
• Subjects: allergic inflammation; Allergies; Allergy and Immunology; Animals; Artificial chromosomes; BAC transgenic mouse; basophils; Basophils - drug effects; Basophils - immunology; Biological and medical sciences; Bone marrow; Bone Marrow Cells - cytology; Cells, Cultured; Cloning; Cytokines; Cytokines - immunology; Cytokines - pharmacology; DsRed fluorochrome; Experiments; Fundamental and applied biological sciences. Psychology; Fundamental immunology; Immunopathology; Interleukin-1 Receptor-Like 1 Protein; Lymphocytes; Mast cells; Mast Cells - drug effects; Mast Cells - immunology; Medical sciences; Mice; Mice, Inbred C57BL; Mice, Transgenic; Receptors, Interleukin - immunology; Receptors, Interleukin-18 - immunology; Rodents; Sarcoidosis. Granulomatous diseases of unproved etiology. Connective tissue diseases. Elastic tissue diseases. Vasculitis; signal transducer and activator of transcription 5; STAT5 Transcription Factor - immunology; Transgenic animals; tyrosine phosphorylation; DsRed fluorochrome; Signal transducer and activator of transcription; allergic inflammation; BAC; signal transducer and activator of transcription 5; Bone marrow–derived mast cell; basophils; Wild-type; Stem cell factor; STAT; BAC transgenic mouse; IL-18R; SCF; Bacterial artificial chromosome; IL-18 receptor; Mast cells; cytokines; tyrosine phosphorylation; WT; BMMC; Allergy; Phosphorylation; Granulocyte; Transgenic animal; Biosynthesis; Basophil; Immunology; Transcription factor STAT5; Interleukin 3; Tyrosine; Immunopathology; Rodentia; Cytokine; Inflammation; Interleukin 13; Vertebrata; Mammalia; Mouse; Aminoacid; Mast cell
• ISSN: 0091-6749; 1097-6825
• DOI: 10.1016/j.jaci.2013.03.033

Background IL-13 is a critical effector cytokine for allergic inflammation. It is produced by several cell types, including mast cells, basophils, and TH 2 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 TH 2 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 TH 2 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 TH 2 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. Conclusion Optimal IL-13 production from mast cells and basophils requires 2 cytokine signals.