Inflammation driven by overexpression of the hypoglycosylated abnormal mucin 1 (MUC1) links inflammatory bowel disease and pancreatitis.
OBJECTIVE
Pancreatitis occurs as an extraintestinal complication of inflammatory bowel disease (IBD), but the cause is poorly understood. Mucin 1 (MUC1) is overexpressed in an abnormal, hypoglycosylated form on the colonic epithelium in human IBD where it contributes to inflammation. MUC1 is also expressed on pancreatic ductal epithelia. We tested the possibility that in IBD, MUC1 expression on pancreatic ducts is also abnormal leading to inflammation and pancreatitis.


METHODS
We used MUC1/interleukin-10 mice that develop IBD. We imaged abnormal MUC1 expression in these mice by adoptively transferring T cells from T cell receptor transgenic mice specific for abnormal MUC1. Cells were labeled with a novel perfluorocarbon tracer reagent and quantified and visualized in vivo using high-throughput F nuclear magnetic resonance spectroscopy and magnetic resonance imaging.


RESULTS
MUC1-specific T cells migrated to the colon in mice with IBD and also to the pancreas. Immunohistochemistry confirmed increased expression on the pancreatic ducts of the abnormal MUC1 seen in the colon and the presence of cellular infiltrate.


CONCLUSIONS
Migration of MUC1-specific T cells to the colon and the pancreas in diseased mice suggests that pancreatitis is an extraintestinal site of IBD, characterized by proinflammatory abnormal expression of MUC1. Therapies directed against abnormal MUC1 have the potential of targeting the disease in both sites.
Kadayakkara
Deepak K
DK
Department of Biological Sciences, Carnegie Mellon University, Pittsburgh, PA, USA.
Beatty
Pamela L
PL
Turner
Michael S
MS
Janjic
Jelena M
JM
Ahrens
Eric T
ET
Finn
Olivera J
OJ
D019264:Adoptive Transfer; D000818:Animals; D005260:Female; D006031:Glycosylation; D007150:Immunohistochemistry; D007249:Inflammation / Q000378:metabolism*; D015212:Inflammatory Bowel Diseases / Q000378:metabolism*; D008279:Magnetic Resonance Imaging; D009682:Magnetic Resonance Spectroscopy; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D008822:Mice, Transgenic; D018396:Mucin-1 / Q000235:genetics / Q000378:metabolism*; D010195:Pancreatitis / Q000378:metabolism*; D013601:T-Lymphocytes / Q000166:cytology / Q000378:metabolism / Q000637:transplantation
D018396:Mucin-1