Colitis Promotes a Pathological Condition of the Liver in the Absence of Foxp3 + Regulatory T Cells.

Autor:	Mathies F; I. Medizinische Klinik und Poliklinik, Universitätsklinikum Hamburg-Eppendorf, 20246 Hamburg, Germany., Steffens N; I. Medizinische Klinik und Poliklinik, Universitätsklinikum Hamburg-Eppendorf, 20246 Hamburg, Germany., Kleinschmidt D; I. Medizinische Klinik und Poliklinik, Universitätsklinikum Hamburg-Eppendorf, 20246 Hamburg, Germany., Stuhlmann F; I. Medizinische Klinik und Poliklinik, Universitätsklinikum Hamburg-Eppendorf, 20246 Hamburg, Germany., Huber FJ; I. Medizinische Klinik und Poliklinik, Universitätsklinikum Hamburg-Eppendorf, 20246 Hamburg, Germany., Roy U; Microbial Immune Regulation Research Group, Helmholtz Centre for Infection Research, 38124 Braunschweig, Germany., Meyer T; Institut für Medizinische Mikrobiologie, Virologie und Hygiene, Universitätsklinikum Hamburg-Eppendorf, 20246 Hamburg, Germany., Luetgehetmann M; Institut für Medizinische Mikrobiologie, Virologie und Hygiene, Universitätsklinikum Hamburg-Eppendorf, 20246 Hamburg, Germany., von Petersdorff M; Institut für Pathologie, Universitätsklinikum Hamburg-Eppendorf, 20246 Hamburg, Germany., Seiz O; I. Medizinische Klinik und Poliklinik, Universitätsklinikum Hamburg-Eppendorf, 20246 Hamburg, Germany., Herkel J; I. Medizinische Klinik und Poliklinik, Universitätsklinikum Hamburg-Eppendorf, 20246 Hamburg, Germany., Schramm C; I. Medizinische Klinik und Poliklinik, Universitätsklinikum Hamburg-Eppendorf, 20246 Hamburg, Germany.; Martin Zeitz Centrum für Seltene Erkrankungen, Universitätsklinikum Hamburg-Eppendorf, 20246 Hamburg, Germany., Flavell RA; Department of Immunobiology, Yale University School of Medicine, New Haven, CT 06520.; Howard Hughes Medical Institute, Yale University School of Medicine, New Haven, CT 06520., Gagliani N; I. Medizinische Klinik und Poliklinik, Universitätsklinikum Hamburg-Eppendorf, 20246 Hamburg, Germany.; Klinik und Poliklinik für Allgemein-, Viszeral- und Thoraxchirurgie, Universitätsklinikum Hamburg-Eppendorf, 20246 Hamburg, Germany.; Immunology and Allergy Unit, Department of Medicine Solna, Karolinska Institute, 17176 Stockholm, Sweden., Krebs C; III. Medizinische Klinik und Poliklinik, Universitätsklinikum Hamburg-Eppendorf, 20246 Hamburg, Germany; and., Panzer U; III. Medizinische Klinik und Poliklinik, Universitätsklinikum Hamburg-Eppendorf, 20246 Hamburg, Germany; and., Abdullah Z; Institute of Experimental Immunology, University Hospital Bonn, 53127 Bonn, Germany., Strowig T; Microbial Immune Regulation Research Group, Helmholtz Centre for Infection Research, 38124 Braunschweig, Germany., Bedke T; I. Medizinische Klinik und Poliklinik, Universitätsklinikum Hamburg-Eppendorf, 20246 Hamburg, Germany., Huber S; I. Medizinische Klinik und Poliklinik, Universitätsklinikum Hamburg-Eppendorf, 20246 Hamburg, Germany; shuber@uke.de.
Jazyk:	angličtina
Zdroj:	Journal of immunology (Baltimore, Md. : 1950) [J Immunol] 2018 Dec 15; Vol. 201 (12), pp. 3558-3568. Date of Electronic Publication: 2018 Nov 16.
DOI:	10.4049/jimmunol.1800711
Abstrakt:	Inflammatory bowel disease is associated with extraintestinal diseases such as primary sclerosing cholangitis in the liver. Interestingly, it is known that an imbalance between Foxp3 + regulatory T cells (Treg) and Th17 cells is involved in inflammatory bowel disease and also in primary sclerosing cholangitis. To explain these associations, one hypothesis is that intestinal inflammation and barrier defects promote liver disease because of the influx of bacteria and inflammatory cells to the liver. However, whether and how this is linked to the Treg and Th17 cell imbalance is unclear. To address this, we used dextran sodium sulfate (DSS) and T cell transfer colitis mouse models. We analyzed the pathological conditions of the intestine and liver on histological, cellular, and molecular levels. We observed bacterial translocation and an influx of inflammatory cells, in particular Th17 cells, to the liver during colitis. In the DSS colitis model, in which Treg were concomitantly increased in the liver, we did not observe an overt pathological condition of the liver. In contrast, the T cell-mediated colitis model, in which Treg are not abundant, was associated with marked liver inflammation and a pathological condition. Of note, upon depletion of Treg in DEREG mice, DSS colitis promotes accumulation of Th17 cells and a pathological condition of the liver. Finally, we studied immune cell migration using KAEDE mice and found that some of these cells had migrated directly from the inflamed intestine into the liver. Overall, these data indicate that colitis can promote a pathological condition of the liver and highlight an important role of Treg in controlling colitis-associated liver inflammation. (Copyright © 2018 by The American Association of Immunologists, Inc.)
Databáze:	MEDLINE
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