P032 Distinct immune cell trigger responses in Ulcerative Colitis – Results from an in vivo human intestinal injury model

Autor: M Bronze, J Vilstrup Johansen, M Attauabi, J Tveiten Bjerrum, M Ramírez Galera, A Woetmann, J Benedict Seidelin
Rok vydání: 2023
Předmět:
Zdroj: Journal of Crohn's and Colitis. 17:i199-i200
ISSN: 1876-4479
1873-9946
DOI: 10.1093/ecco-jcc/jjac190.0162
Popis: Background Ulcerative colitis (UC) is characterized by alternated periods of active inflammation and quiescent disease. The mechanisms behind flare-up reactions are elusive, but it is hypothesized that normally unharmful factors can initiate flares in genetically susceptible individuals with a dysfunctional mucosal barrier and hyper-responsive immune system, leading to sustained inflammation. We aimed to describe the early cellular responses to injury in the normal intestine and in UC patients in remission. Methods Experimental injuries were performed in six UC patients in remission (endoscopic Mayo sub-score 0 and total Mayo score below 3) and in six control subjects1. During the initial sigmoidoscopy, six experimental wounds were made. After 24 and 48 hours, the subjects were re-endoscoped and new biopsies were taken across the experimental injury by angling the biopsy forceps 90° (Figure 1), thus including the mucosa of the injury edge and the wound bed. Biopsies from each time point were sequenced (bulk RNA-sequencing) and the frequencies of different cell types were inferred using deconvolution (Cellanneal)2 Results Type 1-conventional dendritic cells (cDC) and macrophages decreased in both UC and controls after injury (p Conclusion UC patients in complete remission show an increased innate inflammatory response to mucosal injuries compared to healthy individuals, highlighted by the early engagement of inflammatory monocytes, mast cells, and ILCs, particularly ILC3s. Our data show a UC-specific innate cellular hyper-response that may explain the initial mechanisms of flares and could be targeted in future anti-flare therapies. References 1. Seidelin JB et al. Acute Experimental Barrier Injury Triggers Ulcerative Colitis-Specific Innate Hyperresponsiveness and Ulcerative Colitis-Type Microbiome Changes in Humans. Cell Mol Gastroenterol Hepatol 2021;12:1281-1296. 2. Buchauer L, Itzkovitz S. cellanneal: A User-Friendly Deconvolution Software for Omics Data, 2021.
Databáze: OpenAIRE
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