Programmed Death Ligand 1-Expressing Classical Dendritic Cells MitigateHelicobacter-Induced Gastritis.

Autor:	Go DM; Department of Veterinary Pathology, College of Veterinary Medicine, Seoul National University, Seoul, Republic of Korea., Lee SH; Department of Life Sciences, College of Natural Sciences, Research Institute for Natural Sciences, Hanyang University, Seoul, Republic of Korea., Lee SH; Division of Cancer Biology, Research Institute of National Cancer Center, Gyeonggi-do, Republic of Korea., Woo SH; Department of Veterinary Pathology, College of Veterinary Medicine, Seoul National University, Seoul, Republic of Korea., Kim K; Department of Life Sciences, College of Natural Sciences, Research Institute for Natural Sciences, Hanyang University, Seoul, Republic of Korea., Kim K; Department of Life Sciences, College of Natural Sciences, Research Institute for Natural Sciences, Hanyang University, Seoul, Republic of Korea., Park KS; Department of Life Sciences, College of Natural Sciences, Research Institute for Natural Sciences, Hanyang University, Seoul, Republic of Korea., Park JH; Laboratory Animal Medicine, College of Veterinary Medicine, Chonnam National University, Gwangju, Republic of Korea., Ha SJ; Department of Biochemistry, College of Life Science and Biotechnology, Yonsei University, Seoul, Republic of Korea., Kim WH; Department of Pathology, College of Medicine, Seoul National University, Seoul, Republic of Korea., Choi JH; Department of Life Sciences, College of Natural Sciences, Research Institute for Natural Sciences, Hanyang University, Seoul, Republic of Korea. Electronic address: jchoi75@hanyang.ac.kr., Kim DY; Department of Veterinary Pathology, College of Veterinary Medicine, Seoul National University, Seoul, Republic of Korea. Electronic address: daeyong@snu.ac.kr.
Jazyk:	angličtina
Zdroj:	Cellular and molecular gastroenterology and hepatology [Cell Mol Gastroenterol Hepatol] 2021; Vol. 12 (2), pp. 715-739. Date of Electronic Publication: 2021 Apr 21.
DOI:	10.1016/j.jcmgh.2021.04.007
Abstrakt:	Background & Aims: Helicobacter pylori has been reported to modulate local immune responses to colonize persistently in gastric mucosa. Although the induced expression of programmed cell death ligand 1 (PD-L1) has been suggested as an immune modulatory mechanism for persistent infection of H pylori, the main immune cells expressing PD-L1 and their functions in Helicobacter-induced gastritis still remain to be elucidated. Methods: The blockades of PD-L1 with antibody or PD-L1-deficient bone marrow transplantation were performed in Helicobacter-infected mice. The main immune cells expressing PD-L1 in Helicobacter-infected stomach were determined by flow cytometry and immunofluorescence staining. Helicobacter felis or H pylori-infected dendritic cell (DC)-deficient mouse models including Flt3 -/- , Zbtb46-diphtheria toxin receptor, and BDCA2-diphtheria toxin receptor mice were analyzed for pathologic changes and colonization levels. Finally, the location of PD-L1-expressing DCs and the correlation with H pylori infection were analyzed in human gastric tissues using multiplexed immunohistochemistry. Results: Genetic or antibody-mediated blockade of PD-L1 aggravated Helicobacter-induced gastritis with mucosal metaplasia. Gastric classical DCs expressed considerably higher levels of PD-L1 than other immune cells and co-localized with T cells in gastritis lesions from Helicobacter-infected mice and human beings. H felis- or H pylori-infected Flt3 -/- or classical DC-depleted mice showed aggravated gastritis with severe T-cell and neutrophil accumulation with low bacterial loads compared with that in control mice. Finally, PD-L1-expressing DCs were co-localized with T cells and showed a positive correlation with H pylori infection in human subjects. Conclusions: The PD-1/PD-L1 pathway may be responsible for the immune modulatory function of gastric DCs that protects the gastric mucosa from Helicobacter-induced inflammation, but allows persistent Helicobacter colonization. (Copyright © 2021 The Authors. Published by Elsevier Inc. All rights reserved.)
Databáze:	MEDLINE
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