The role of Intestinal tissue macrophages in the pathogenesis of Inflammatory Bowel Disease

Abstract

The inflammatory bowel diseases, Crohn’s disease (CD) and Ulcerative colitis (UC) are chronic relapsing remitting inflammatory diseases of the gastrointestinal tract. Over the last 20 years significant advances in the scientific understanding of these complex diseases has been made and several new pharmacological therapies with new mechanisms of action are now available. It is accepted that the inflammatory bowel diseases result from a complex interaction between environmental factors, host genetics, the immune system responses and the intestinal microbiota. Evidence from genetic, animal and human studies have identified a key role for the innate immune system in the pathogenesis of these diseases. Although several mouse studies have implicated mechanisms by which intestinal macrophages may be involved in inflammatory bowel disease pathogenesis, data from humans with the disease is sparse. In this study we have recruited patients with ulcerative colitis and colonic Crohn’s disease as well as a group of health controls. In these patients we have isolated intestinal tissue macrophages and subjected the RNA from these cells to high throughput RNA-Seq. We have demonstrated that the gene expression profiles of the IBD macrophages are profoundly altered. We have found that in IBD patients the macrophages promote inflammation, recruitment of T-cells through the release of chemokines such as CXCL9 & CXCL10 and that cellular metabolic process are down regulated in these cells. We were able to show that although the macrophages from UC and CD have similar gene expression there are important differences such as expression of the M2 phenotype, up-regulation of pathways associated with fibrosis and granuloma formation in CD but not the UC macrophages.

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Identifiers

ORCID for Tilman Sanchez-Elsner: orcid.org/0000-0003-1915-2410

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