Plos One Research Article. Fibrosis is a serious consequence of Crohn’s disease (CD), often necessitating surgical resection. Research study examined the hypothesis that IL-13 may promote collagen accumulation within the CD muscle microenvironment. (Not written in layman terms. Written using medical terminology which may be confusing for some to understand)
PLOS ONE: IL-13 Promotes Collagen Accumulation in Crohn’s Disease Fibrosis by Down-Regulation of Fibroblast MMP Synthesis: A Role for Innate Lymphoid Cells?:
PLOS ONE: IL-13 Promotes Collagen Accumulation in Crohn’s Disease Fibrosis by Down-Regulation of Fibroblast MMP Synthesis: A Role for Innate Lymphoid Cells?:
Abstract
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.
Citation: Bailey JR, Bland PW, Tarlton JF, Peters I, Moorghen M, et al. (2012) IL-13 Promotes Collagen Accumulation in Crohn’s Disease Fibrosis by Down-Regulation of Fibroblast MMP Synthesis: A Role for Innate Lymphoid Cells? PLoS ONE 7(12): e52332. doi:10.1371/journal.pone.0052332
Editor: Niels Olsen Saraiva Câmara, Universidade de Sao Paulo, Brazil
Received: August 8, 2012; Accepted: November 12, 2012; Published: December 31, 2012
Copyright: © 2012 Bailey et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
Funding: This work was supported by Action Medical Research, SP4260 (http://www.action.org.uk); National Association for Colitis and Crohn’s disease, M/07/5 (http://www.nacc.org.uk); Swedish Fund for Strategic Research (http://www.stratresearch.se/en/), and Edith Lidiard Private Bequest. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.
Competing interests: The authors have declared that no competing interests exist.
* E-mail: John.Tarlton@bris.ac.uk
