Activated regulatory T-cells promote duodenal bacterial translocation into necrotic areas in severe acute pancreatitis.

Autor:	Glaubitz J; Department of Medicine A, university medicine Greifswald, Greifswald, Germany., Wilden A; Department of Medicine A, university medicine Greifswald, Greifswald, Germany., Frost F; Department of Medicine A, university medicine Greifswald, Greifswald, Germany., Ameling S; Interfaculty Institute for Genetics and Functional Genomics, Department of Functional Genomics, University Medicine Greifswald, Greifswald, Germany., Homuth G; Interfaculty Institute for Genetics and Functional Genomics, Department of Functional Genomics, University Medicine Greifswald, Greifswald, Germany., Mazloum H; Department of Medicine A, university medicine Greifswald, Greifswald, Germany., Rühlemann MC; Institute of Clinical Molecular Biology, Christian-Albrechts-Universität zu Kiel, Kiel, Germany.; Hannover Medical School, Institute for Medical Microbiology and Hospital Epidemiology, Hannover, Germany., Bang C; Institute of Clinical Molecular Biology, Christian-Albrechts-Universität zu Kiel, Kiel, Germany., Aghdassi AA; Department of Medicine A, university medicine Greifswald, Greifswald, Germany., Budde C; Department of Medicine A, university medicine Greifswald, Greifswald, Germany., Pickartz T; Department of Medicine A, university medicine Greifswald, Greifswald, Germany., Franke A; Institute of Clinical Molecular Biology, Christian-Albrechts-Universität zu Kiel, Kiel, Germany., Bröker BM; Department of Immunology, Universitätsmedizin Greifswald, Greifswald, Germany., Voelker U; Interfaculty Institute for Genetics and Functional Genomics, Department of Functional Genomics, University Medicine Greifswald, Greifswald, Germany., Mayerle J; Medizinische Klinik und Poliklinik 2, Klinikum der Universitat Munchen, Munchen, Germany., Lerch MM; Department of Medicine A, university medicine Greifswald, Greifswald, Germany., Weiss FU; Department of Medicine A, university medicine Greifswald, Greifswald, Germany., Sendler M; Department of Medicine A, university medicine Greifswald, Greifswald, Germany matthias.sendler@uni-greifswald.de.
Jazyk:	angličtina
Zdroj:	Gut [Gut] 2023 Jul; Vol. 72 (7), pp. 1355-1369. Date of Electronic Publication: 2023 Jan 11.
DOI:	10.1136/gutjnl-2022-327448
Abstrakt:	Objective: In acute pancreatitis (AP), bacterial translocation and subsequent infection of pancreatic necrosis are the main risk factors for severe disease and late death. Understanding how immunological host defence mechanisms fail to protect the intestinal barrier is of great importance in reducing the mortality risk of the disease. Here, we studied the role of the T reg /Th17 balance for maintaining the intestinal barrier function in a mouse model of severe AP. Design: AP was induced by partial duct ligation in C57Bl/6 or DEREG mice, in which regulatory T-cells (T reg ) were depleted by intraperitoneal injection of diphtheria toxin. By flow cytometry, functional suppression assays and transcriptional profiling we analysed T reg activation and characterised T-cells of the lamina propria as well as intraepithelial lymphocytes (IELs) regarding their activation and differentiation. Microbiota composition was examined in intestinal samples as well as in murine and human pancreatic necrosis by 16S rRNA gene sequencing. Results: The prophylactic T reg- depletion enhanced the proinflammatory response in an experimental mouse model of AP but stabilised the intestinal immunological barrier function of Th17 cells and CD8 + /γδTCR + IELs. T reg depleted animals developed less bacterial translocation to the pancreas. Duodenal overgrowth of the facultative pathogenic taxa Escherichia/Shigella which associates with severe disease and infected necrosis was diminished in T reg depleted animals. Conclusion: T regs play a crucial role in the counterbalance against systemic inflammatory response syndrome. In AP, T reg -activation disturbs the duodenal barrier function and permits translocation of commensal bacteria into pancreatic necrosis. Targeting T regs in AP may help to ameliorate the disease course. Competing Interests: Competing interests: None declared. (© Author(s) (or their employer(s)) 2023. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)
Databáze:	MEDLINE
Externí odkaz:	Zobrazit plný text záznamu