| First Author | Luzina IG | Year | 2012 |
| Journal | J Immunol | Volume | 189 |
| Issue | 1 | Pages | 403-10 |
| PubMed ID | 22634619 | Mgi Jnum | J:188951 |
| Mgi Id | MGI:5442659 | Doi | 10.4049/jimmunol.1200259 |
| Citation | Luzina IG, et al. (2012) Full-length IL-33 promotes inflammation but not Th2 response in vivo in an ST2-independent fashion. J Immunol 189(1):403-10 |
| abstractText | Expression of IL-33 is elevated in patients with pulmonary diseases, and full-length (not proteolytically processed) IL-33 is the predominant form in the lungs in health and disease. To determine whether activation of IL-33 is needed for functional effects, activities of full-length mouse and mature mouse (mm) forms of IL-33 were compared in vivo. Replication-deficient adenoviral constructs were used for gene delivery. Both isoforms caused pulmonary infiltration of lymphocytes and neutrophils, whereas mm IL-33 also caused pulmonary eosinophilia and goblet cell hyperplasia and increased expression of IL-4, IL-5, IL-13, IL-17, MCP-1, and KC. The different effects were not associated with differential release from IL-33-producing cells or by differences in subcellular distributions of IL-33 isoforms. Germline deficiency of the cell surface receptor chain ST2 abrogated the mm IL-33-induced Th2-associated effects (pulmonary eosinophilia, goblet cell hyperplasia, and increased IL-4 and IL-5), yet the lymphocytic infiltration induced by full-length mouse IL-33 or mm IL-33 was not fully abrogated by the absence of ST2. The similar effects of IL-33 isoforms were associated with comparable regulation of gene expression, notably matrix metalloproteinases 3, 10, and 13. Thus, full-length IL-33 is functionally active in vivo in an ST2-independent fashion, and its effects are partially different from those of mature IL-33. The different effects of these isoforms, particularly the pro-Th2 effects of mature IL-33, are due to differential utilization of the IL-33R chain ST2, whereas their similar effects result from regulation of gene expression. |
