Efficient cytokine-induced IL-13 production by mast cells requires both IL-33 and IL-3 - 02/09/13
, Cynthia Watson, BSc a, ∗, Laura Kummola, MSc b, Xi Chen, MD a, Jane Hu-Li, BSc a, Liying Guo, PhD a, Ryoji Yagi, PhD a, William E. Paul, MD a, ⁎ 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.
Conclusion |
Optimal IL-13 production from mast cells and basophils requires 2 cytokine signals.
Le texte complet de cet article est disponible en PDF.Key words : Mast cells, basophils, allergic inflammation, cytokines, signal transducer and activator of transcription 5, tyrosine phosphorylation, BAC transgenic mouse, DsRed fluorochrome
Abbreviations used : BAC, BMMC, IL-18R, SCF, STAT, WT
Plan
| Supported by the National Institute of Allergy and Infectious Diseases Intramural Program (to I.S.J., C.W., X.C., J.H.-L., L.G., R.Y., and W.E.P.), the Finnish Medical Foundation (to I.S.J.), Competitive Research Funding of the Tampere University Hospital (grant 9N018, to I.S.J.), the Sigrid Juselius Foundation (to I.S.J. and L.K.), and Fimlab laboratories (grant X51409, to I.S.J.). |
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| Disclosure of potential conflict of interest: I. S. Junttila has been supported by one or more grants from Competitive Research Funding of Tampere University Hospital, Fimlab Laboratories, and the Sigrid Juselius Foundation. L. Kummola has been supported by one or more grants from the Sigrig Juselius Foundation. The rest of the authors declare that they have no relevant conflicts of interest. |
Vol 132 - N° 3
P. 704 - septembre 2013 Retour au numéro
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