Gut and liver T-cells of common clonal origin in primary sclerosing cholangitis-inflammatory bowel disease

Abstract

Primary sclerosing cholangitis (PSC) is a devastating liver disease strongly associated with inflammatory bowel disease (IBD). The cause of PSC is unknown, but it has been suggested that the immune reactions in the gut and the liver are connected. Our data demonstrate for the first time that a proportion of the T-cells in the gut and the liver react to similar triggers, and that this proportion is particularly high in patients with PSC and IBD.

Gut and Liver B Cells of Common Clonal Origin in Primary Sclerosing Cholangitis–Inflammatory Bowel Disease

“…Similar to our previous work on gut and liver T‐cell clonality in PSC‐IBD, we found that the productive clonality of the gut and liver B‐cell compartment to range from 0.04 to 0.16, values that are higher than those reported in the blood of patients with systemic lupus erythematosus and comparable with those observed in the pancreatic draining lymph nodes of patients with type 1 diabetes . These findings suggest that B cells in the gut and liver of patients with PSC‐IBD are more oligoclonal and expanded compared to those in the periphery and support further study of gut and liver tissue as a means of determining potential antigenic triggers in PSC‐IBD.…”

“…Activated lymphocytes responding to microbial products (antigens, metabolites, toxins) circulating within the enterohepatic axis might be disease relevant as patients with PSC‐IBD show a distinct microbiota in the gut compared to patients with ulcerative colitis and healthy controls . Supporting this hypothesis, we have detected that a greater number and proportion of gut and liver T cells share a common clonal origin in patients with PSC‐IBD compared to non‐PSC‐IBD controls . These findings suggest immune cells migrating from the gut to the liver drive hepatic inflammation and antigens shared between both tissue compartments may trigger the activation of adaptive immunity in PSC‐IBD.…”

“…Although public gut–liver clonotypes were absent among unpaired gut and liver samples, private B‐cell clonotypes in paired samples constituted 8.3% (range, 1.6%‐18.0%) (Fig. D) of the total gut and liver B‐cell clonotypes, whereas private T‐cell clonotypes represented on average 32.0% ± 11.7% of the total T‐cell clonotypes, a higher frequency then previously reported as clonotypes detected in matched blood samples at a frequency of less than 0.01% were not excluded in this study given BCR clonality in blood was not analyzed (Supporting Fig.). Private gut–liver B‐cell clonotypes appeared as a higher proportion of the total gut clonotypes in 5/10 samples and represented a greater proportion of the liver compartment in the remaining 5/10 samples (Fig.…”

“…Paired, snap‐frozen, inflamed colonic biopsies from the ascending colon (1‐5 mg) and explanted liver tissue (50‐60 mg) from a Norwegian cohort of patients with PCS‐IBD (n = 10) were used in this study (see Table for detailed clinical characteristics of the PSC‐IBD study cohort at the time of sample collection). Genomic DNA isolated from the same tissue samples was previously used to study shared T‐cell clonality in the gut and liver of patients with PSC‐IBD . PSC was diagnosed on the basis of accepted criteria with typical findings of bile duct irregularities on cholangiography .…”

Xia-Yu-Xue Decoction Inhibits Intestinal Epithelial Cell Apoptosis in CCl4-Induced Liver Fibrosis

“…Primary sclerosing cholangitis (PSC) is a devastating liver disease strongly associated with inflammatory bowel disease (IBD). It has been suggested a crosstalk of the immune reactions between the gut and the liver [24]. It has also been reported that abnormal composition of gut microbiota was observed in patients with cystic fibrosis [25].…”