| First Author | Rankin AL | Year | 2010 |
| Journal | J Immunol | Volume | 184 |
| Issue | 3 | Pages | 1526-35 |
| PubMed ID | 20042577 | Mgi Jnum | J:159528 |
| Mgi Id | MGI:4443227 | Doi | 10.4049/jimmunol.0903306 |
| Citation | Rankin AL, et al. (2010) IL-33 induces IL-13-dependent cutaneous fibrosis. J Immunol 184(3):1526-35 |
| abstractText | IL-33 is constitutively expressed in epithelial barrier tissues, such as skin. Although increased expression of IL-33/IL-33R has been correlated with fibrotic disorders, such as scleroderma and progressive systemic sclerosis, the direct consequences of IL-33 release in skin has not been reported. To determine the effects of dysregulated IL-33 signaling in skin, we administered IL-33 s.c. and monitored its effects at the injection site. Administration of IL-33 resulted in IL-33R-dependent accumulation of eosinophils, CD3(+) lymphocytes, F4/80(+) mononuclear cells, increased expression of IL-13 mRNA, and the development of cutaneous fibrosis. Consistent with extensive cutaneous tissue remodeling, IL-33 resulted in significant modulation of a number of extracellular matrix-associated genes, including collagen VI, collagen III, and tissue inhibitor of metalloproteases-1. We establish that IL-33-induced fibrosis requires IL-13 using IL-13 knockout mice and eosinophils using Delta dblGATA mice. We show that bone marrow-derived eosinophils secrete IL-13 in response to IL-33 stimulation, suggesting that eosinophil-derived IL-13 may promote IL-33-induced cutaneous fibrosis. Collectively, our results identify IL-33 as a previously unrecognized profibrotic mediator in skin and highlight the cellular and molecular pathways by which this pathology develops. |
