IL-33 Induces a Hyporesponsive Phenotype in Human and Mouse Mast Cells
| Autor: | Jeong Han Kang, Shoko Iwaki, Marcus V. Andrade, Alasdair M. Gilfillan, Jared M. Brown, Daniel Smrž, Susana C. Hilderbrand, Tomonobu Ito, Avanti Desai, Dean D. Metcalfe, Mi-Yeon Jung, Geethani Bandara, Michael A. Beaven |
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| Rok vydání: | 2013 |
| Předmět: |
Immunology
Interleukin-1 Receptor-Like 1 Protein Bone Marrow Cells Biology Article Pathogenesis Mice Downregulation and upregulation medicine Animals Humans Immunology and Allergy Mast Cells Receptor Immunosuppression Therapy Mice Knockout Phospholipase C gamma Interleukins Interleukin Receptors Interleukin Interleukin-33 Mast cell Phenotype Actins Interleukin 33 medicine.anatomical_structure Myeloid Differentiation Factor 88 Proto-Oncogene Proteins c-hck Protein Multimerization |
| Zdroj: | The Journal of Immunology. 190:531-538 |
| ISSN: | 1550-6606 0022-1767 |
| Popis: | IL-33 is elevated in afflicted tissues of patients with mast cell (MC)–dependent chronic allergic diseases. Based on its acute effects on mouse MCs, IL-33 is thought to play a role in the pathogenesis of allergic disease through MC activation. However, the manifestations of prolonged IL-33 exposure on human MC function, which best reflect the conditions associated with chronic allergic disease, are unknown. In this study, we found that long-term exposure of human and mouse MCs to IL-33 results in a substantial reduction of MC activation in response to Ag. This reduction required >72 h exposure to IL-33 for onset and 1–2 wk for reversion following IL-33 removal. This hyporesponsive phenotype was determined to be a consequence of MyD88-dependent attenuation of signaling processes necessary for MC activation, including Ag-mediated calcium mobilization and cytoskeletal reorganization, potentially as a consequence of downregulation of the expression of phospholipase Cγ1 and Hck. These findings suggest that IL-33 may play a protective, rather than a causative, role in MC activation under chronic conditions and, furthermore, reveal regulated plasticity in the MC activation phenotype. The ability to downregulate MC activation in this manner may provide alternative approaches for treatment of MC-driven disease. |
| Databáze: | OpenAIRE |
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