Homing of mucosal lymphocytes to the liver in the pathogenesis of hepatic complications of inflammatory bowel disease.
Primary sclerosing cholangitis is strongly linked to inflammatory bowel disease, but any model to explain the development of primary sclerosing cholangitis must take into account the fact that it usually runs a course independent from inflammation in the bowel, illustrated by the fact that this disease can develop many years after proctocolectomy. Thus, liver disease can develop in the absence of a diseased colon and cannot be explained solely by release of toxic factors from the inflamed gut. We propose the existence of an enterohepatic circulation of lymphocytes, whereby some mucosal lymphocytes generated in the gut during active inflammatory disease subsequently persist as longlived memory cells capable of recirculation through the liver. Under the right conditions, these dual-homing lymphocytes might become activated in the liver resulting in hepatic inflammation that is independent from inflammation in the gut. Recent reports that some lymphocyte homing-receptors are shared by the liver and gut provide a molecular basis for this hypothesis and explain the distribution of extraintestinal disease in inflammatory bowel disease.
Grant
Allister J
AJ
Liver Research Laboratories, University of Birmingham Institute of Clinical Science, MRC Centre for Immune Regulation, Queen Elizabeth Hospital, Edgbaston, B15 2TT, Birmingham, UK.
Lalor
Patricia F
PF
Salmi
Marko
M
Jalkanen
Sirpa
S
Adams
David H
DH
D015815:Cell Adhesion Molecules; D015209:Cholangitis, Sclerosing / Q000209:etiology* / Q000276:immunology*; D004764:Enterohepatic Circulation / Q000276:immunology*; D006801:Humans; D007136:Immunoglobulins / Q000276:immunology; D007156:Immunologic Memory / Q000276:immunology*; D007249:Inflammation; D015212:Inflammatory Bowel Diseases / Q000150:complications* / Q000276:immunology*; D007413:Intestinal Mucosa / Q000166:cytology / Q000276:immunology*; D008107:Liver Diseases / Q000209:etiology* / Q000276:immunology*; D008213:Lymphocyte Activation / Q000276:immunology*; D009088:Mucoproteins / Q000276:immunology; D016201:Receptors, Lymphocyte Homing / Q000276:immunology*; D019087:Selectins / Q000276:immunology; D015398:Signal Transduction / Q000276:immunology; D013601:T-Lymphocytes / Q000276:immunology*; D015854:Up-Regulation / Q000276:immunology
D015815:Cell Adhesion Molecules; D007136:Immunoglobulins; C504265:MADCAM1 protein, human; D009088:Mucoproteins; D016201:Receptors, Lymphocyte Homing; D019087:Selectins