Abstract
In the healthy colon, intestinal epithelial cells (IEC) form a physical barrier separating the myriad of gut Ags from the cells of the immune system. Simultaneously, IEC use several mechanisms to actively maintain immunologic tolerance to nonpathogenic Ags, including commensal bacteria. However, during inflammatory bowel disease (IBD), the line of defense provided by IEC is breached, resulting in uncontrolled immune responses. As IEC are a principal mediator of immune responses in the gut, we were interested in discerning the gene expression pattern of IEC during development and progression of IBD. Laser capture microdissection and microarray analysis were combined to identify the LY6 superfamily as strongly up-regulated genes in inflamed IEC of the colon in two models of murine colitis. Surface expression of LY6A and LY6C on IEC is induced by several cytokines present within the colitic gut, including IL-22 and IFN-γ. Furthermore, cross-linking of LY6C results in production of a number of chemokines which are known to be involved in the immunopathogenesis of IBD. Increased chemokine production was cholesterol dependent, suggesting a role for lipid raft structures in the mechanism. As such, LY6 molecules represent novel targets to down-regulate chemokine expression in the colon and limit subsequent inflammation associated with IBD.
| Original language | English (US) |
|---|---|
| Pages (from-to) | 3874-3881 |
| Number of pages | 8 |
| Journal | Journal of Immunology |
| Volume | 180 |
| Issue number | 6 |
| DOIs | |
| State | Published - Mar 15 2008 |
| Externally published | Yes |
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ASJC Scopus subject areas
- Immunology
Cite this
Intestinal epithelial cell up-regulation of LY6 molecules during colitis results in enhanced chemokine secretion. / Flanagan, Ken; Modrusan, Zora; Ochoa, Jennine; Chavali, Arvind; Kasman, Ian; Komuves, Laszlo; Mo, Lian; Diehl, Lauri.
In: Journal of Immunology, Vol. 180, No. 6, 15.03.2008, p. 3874-3881.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Intestinal epithelial cell up-regulation of LY6 molecules during colitis results in enhanced chemokine secretion
AU - Flanagan, Ken
AU - Modrusan, Zora
AU - Ochoa, Jennine
AU - Chavali, Arvind
AU - Kasman, Ian
AU - Komuves, Laszlo
AU - Mo, Lian
AU - Diehl, Lauri
PY - 2008/3/15
Y1 - 2008/3/15
N2 - In the healthy colon, intestinal epithelial cells (IEC) form a physical barrier separating the myriad of gut Ags from the cells of the immune system. Simultaneously, IEC use several mechanisms to actively maintain immunologic tolerance to nonpathogenic Ags, including commensal bacteria. However, during inflammatory bowel disease (IBD), the line of defense provided by IEC is breached, resulting in uncontrolled immune responses. As IEC are a principal mediator of immune responses in the gut, we were interested in discerning the gene expression pattern of IEC during development and progression of IBD. Laser capture microdissection and microarray analysis were combined to identify the LY6 superfamily as strongly up-regulated genes in inflamed IEC of the colon in two models of murine colitis. Surface expression of LY6A and LY6C on IEC is induced by several cytokines present within the colitic gut, including IL-22 and IFN-γ. Furthermore, cross-linking of LY6C results in production of a number of chemokines which are known to be involved in the immunopathogenesis of IBD. Increased chemokine production was cholesterol dependent, suggesting a role for lipid raft structures in the mechanism. As such, LY6 molecules represent novel targets to down-regulate chemokine expression in the colon and limit subsequent inflammation associated with IBD.
AB - In the healthy colon, intestinal epithelial cells (IEC) form a physical barrier separating the myriad of gut Ags from the cells of the immune system. Simultaneously, IEC use several mechanisms to actively maintain immunologic tolerance to nonpathogenic Ags, including commensal bacteria. However, during inflammatory bowel disease (IBD), the line of defense provided by IEC is breached, resulting in uncontrolled immune responses. As IEC are a principal mediator of immune responses in the gut, we were interested in discerning the gene expression pattern of IEC during development and progression of IBD. Laser capture microdissection and microarray analysis were combined to identify the LY6 superfamily as strongly up-regulated genes in inflamed IEC of the colon in two models of murine colitis. Surface expression of LY6A and LY6C on IEC is induced by several cytokines present within the colitic gut, including IL-22 and IFN-γ. Furthermore, cross-linking of LY6C results in production of a number of chemokines which are known to be involved in the immunopathogenesis of IBD. Increased chemokine production was cholesterol dependent, suggesting a role for lipid raft structures in the mechanism. As such, LY6 molecules represent novel targets to down-regulate chemokine expression in the colon and limit subsequent inflammation associated with IBD.
UR - http://www.scopus.com/inward/record.url?scp=44849086588&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=44849086588&partnerID=8YFLogxK
U2 - 10.4049/jimmunol.180.6.3874
DO - 10.4049/jimmunol.180.6.3874
M3 - Article
C2 - 18322195
AN - SCOPUS:44849086588
VL - 180
SP - 3874
EP - 3881
JO - Journal of Immunology
JF - Journal of Immunology
SN - 0022-1767
IS - 6
ER -