Preprint Review Version 1 Preserved in Portico This version is not peer-reviewed

CCR6-CCL20 Signalling Networks in Inflammatory Bowel Disease

Version 1 : Received: 17 July 2018 / Approved: 17 July 2018 / Online: 17 July 2018 (10:37:41 CEST)

A peer-reviewed article of this Preprint also exists.

Ranasinghe, R.; Eri, R. CCR6–CCL20-Mediated Immunologic Pathways in Inflammatory Bowel Disease. Gastrointest. Disord. 2018, 1, 15-29. Ranasinghe, R.; Eri, R. CCR6–CCL20-Mediated Immunologic Pathways in Inflammatory Bowel Disease. Gastrointest. Disord. 2018, 1, 15-29.

Abstract

Inflammatory bowel disease (IBD) has evoked a significant interest in human immunobiology given its tactical immune evasion methodologies resulting in acute immune destabilization. IBD comprising of Crohn’s disease and Ulcerative colitis manifest as chronic inflammation in the gut mucosa, leading to complexities involving immune dysregulation in the T helper lymphocyte arm effecting disease pathogenicity. The mucosa of the alimentary canal is constantly exposed to a myriad of food antigens and luminal microorganisms for which a consistent host-protective mechanism is operative in healthy people. Lowered mucosal immune expression which allows penetration of the epithelial barrier by infective pathogenic microbes, elicits both innate and adaptive immune responses in the gut culminating in aberrant intestinal inflammation. Interestingly, IBD leukocyte repertoire is significantly entwined with chemokine assisted chemotactic navigation into the sites of inflammation which is also thought to generate favourable immune suppressive responses. The functions of the cognate chemokine receptor, CCR6, which binds with its unique ligand CCL20, are expected to tilt the balance between upregulation of homeostatic tolerance and inflammatory pathophysiology. This review aims at critically examining the CCR6 driven immune pathways; TH1/TH2, TH1/TH17, TH17/ Treg, IL-23/IL-17, Akt/ERK-1 /2, ILC3 for systematic investigation of its underlying mechanisms in the future and to underpin its importance in resolving IBD aetiopathology. Thus, CCR6 occupies an exclusive position in gut immunology which renders it an invaluable therapeutic tool for the production of novel medicaments to treat IBD.

Keywords

IBD; CCR6; CCL20; Immune mechanisms; T helper lymphocytes

Subject

Biology and Life Sciences, Immunology and Microbiology

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