IL-13 Promotes Collagen Accumulation in Crohn’s Disease Fibrosis by Down-Regulation of Fibroblast MMP Synthesis: A Role for Innate Lymphoid Cells?
| Autor: | Chris Probert, P A Sylvester, John F Tarlton, Christine V. Whiting, Iain R. Peters, Moganaden Moorghen, Paul W. Bland, Jennifer R Bailey |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2012 |
| Předmět: |
Male
Pathology lcsh:Medicine NK cells Crohn Disease Fibrosis Molecular Cell Biology Myocyte Membrane Receptor Signaling Lymphocytes Intestinal Mucosa lcsh:Science education.field_of_study Multidisciplinary Interleukin-13 Muscles Innate lymphoid cell Immune cells Middle Aged Interleukin-13 Receptor alpha1 Subunit Extracellular Matrix medicine.anatomical_structure Connective Tissue Interleukin 13 Cytokines Medicine Female Collagen Immunologic Receptor Signaling Research Article Signal Transduction Muscle tissue Adult medicine.medical_specialty Adolescent Population Immunology Down-Regulation Immunopathology Gastroenterology and Hepatology Biology Young Adult medicine Humans education Fibroblast Aged lcsh:R Inflammatory Bowel Disease Fibroblasts medicine.disease Molecular biology Extracellular Matrix Composition Matrix Metalloproteinases Cell culture Immune System lcsh:Q |
| Zdroj: | PLoS ONE University of Bristol-PURE PLoS ONE, Vol 7, Iss 12, p e52332 (2012) |
| ISSN: | 1932-6203 |
| Popis: | Background Fibrosis is a serious consequence of Crohn’s disease (CD), often necessitating surgical resection. We examined the hypothesis that IL-13 may promote collagen accumulation within the CD muscle microenvironment. Methods Factors potentially modulating collagen deposition were examined in intestinal tissue samples from fibrotic (f) CD and compared with cancer control (C), ulcerative colitis (UC) and uninvolved (u) CD. Mechanisms attributable to IL-13 were analysed using cell lines derived from uninvolved muscle tissue and tissue explants. Results In fCD muscle extracts, collagen synthesis was significantly increased compared to other groups, but MMP-2 was not co-ordinately increased. IL-13 transcripts were highest in fCD muscle compared to muscle from other groups. IL-13 receptor (R) α1 was expressed by intestinal muscle smooth muscle, nerve and KIR+ cells. Fibroblasts from intestinal muscle expressed Rα1, phosphorylated STAT6 in response to IL-13, and subsequently down-regulated MMP-2 and TNF-α-induced MMP-1 and MMP-9 synthesis. Cells with the phenotype KIR+CD45+CD56+/−CD3− were significantly increased in fCD muscle compared to all other groups, expressed Rα1 and membrane IL-13, and transcribed high levels of IL-13. In explanted CD muscle, these cells did not phosphorylate STAT6 in response to exogenous IL-13. Conclusions The data indicate that in fibrotic intestinal muscle of Crohn’s patients, the IL-13 pathway is stimulated, involving a novel population of infiltrating IL-13Rα1+, KIR+ innate lymphoid cells, producing IL-13 which inhibits fibroblast MMP synthesis. Consequently, matrix degradation is down-regulated and this leads to excessive collagen deposition. |
| Databáze: | OpenAIRE |
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