Inflammation Driven by Overexpression of the Hypoglycosylated Abnormal Mucin 1 (MUC1) Links Inflammatory Bowel Disease and Pancreatitis

Abstract

Objectives-Pancreatitis occurs as extraintestinal complication of IBD but the cause is poorly understood. 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+/IL-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 19 F NMR spectroscopy and MRI.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 pro-inflammatory abnormal expression of MUC1. Therapies directed against abnormal MUC1 have the potential of targeting the disease in both sites.

Rapid quantification of inflammation in tissue samples using perfluorocarbon emulsion and fluorine-19 nuclear magnetic resonance

“…These same whole-tissue NMR methods can also be useful for ‘counting’ transplanted therapeutic or diagnostic cells that have been labeled with PFC emulsion ex vivo prior to transfer in vivo (13,23). A multitude of regenerative medicine and immunotherapeutic cell therapy studies could benefit from a tool that does not rely on laborious histology or flow cytometry to accurately assay cell biodistribution in tissue panels.…”

“…Moreover, ex vivo labeled, phenotypically defined, immune cells can also be used for inflammation diagnostic purposes when infused into a subject. Using ex vivo labeling approaches, the mean PFC uptake, expressed as 19 F/cell, is often measured as part of the cell labeling protocol development (13), and this parameter can be used to calculate the apparent number of cells present in tissue samples directly from the 19 F NMR data (13,23). …”

Tumor-infiltrating neutrophils in pancreatic neoplasia

“…23 MUC1 is known to 24 promote inflammation 25 by acting as a powerful chemoattractant for the innate immune system 17,26–27 and reported to drive the progression to colitis-associated colon cancer 17 through cytokine and oxygen metabolite production. 21,22 …”

Design and Development of Theranostic Nanomedicines

“…low droplet size of nanoemulsions (150-200 nm) facilitates passive targeting to tumors and easy penetration to inflamed tissues via epr effect. passive targeting to circulating inflammatory cells by pFC nanoemulsions has been extensively investigated for the purpose of 19 F Mri of inflammation [119,[127][128][129] and potentially drug delivery to inflamed tissues [3]. a recent study used pFC nanoemulsions to deliver antigen to dendritic cells with the goal of boosting the immune response in DC-based vaccines [130].…”