Programmed Death Ligand 1-Expressing Classical Dendritic Cells Mitigate Helicobacter-Induced GastritisSummary
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...
| Main Authors: | , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Elsevier
2021-01-01
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| Series: | Cellular and Molecular Gastroenterology and Hepatology |
| Subjects: | |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S2352345X21000783 |
| _version_ | 1818655532501696512 |
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| author | Du-Min Go Seung Hyun Lee Su-Hyung Lee Sang-Ho Woo Kibyeong Kim Kyeongdae Kim Kyu Seong Park Jong-Hwan Park Sang-Jun Ha Woo Ho Kim Jae-Hoon Choi Dae-Yong Kim |
| author_facet | Du-Min Go Seung Hyun Lee Su-Hyung Lee Sang-Ho Woo Kibyeong Kim Kyeongdae Kim Kyu Seong Park Jong-Hwan Park Sang-Jun Ha Woo Ho Kim Jae-Hoon Choi Dae-Yong Kim |
| author_sort | Du-Min Go |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-12-17T03:11:11Z |
| format | Article |
| id | doaj.art-580db00f1d92496ebdade146c668095b |
| institution | Directory Open Access Journal |
| issn | 2352-345X |
| language | English |
| last_indexed | 2024-12-17T03:11:11Z |
| publishDate | 2021-01-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Cellular and Molecular Gastroenterology and Hepatology |
| spelling | doaj.art-580db00f1d92496ebdade146c668095b2022-12-21T22:05:50ZengElsevierCellular and Molecular Gastroenterology and Hepatology2352-345X2021-01-01122715739Programmed Death Ligand 1-Expressing Classical Dendritic Cells Mitigate Helicobacter-Induced GastritisSummaryDu-Min Go0Seung Hyun Lee1Su-Hyung Lee2Sang-Ho Woo3Kibyeong Kim4Kyeongdae Kim5Kyu Seong Park6Jong-Hwan Park7Sang-Jun Ha8Woo Ho Kim9Jae-Hoon Choi10Dae-Yong Kim11Department of Veterinary Pathology, College of Veterinary Medicine, Seoul National University, Seoul, Republic of KoreaDepartment of Life Sciences, College of Natural Sciences, Research Institute for Natural Sciences, Hanyang University, Seoul, Republic of KoreaDivision of Cancer Biology, Research Institute of National Cancer Center, Gyeonggi-do, Republic of KoreaDepartment of Veterinary Pathology, College of Veterinary Medicine, Seoul National University, Seoul, Republic of KoreaDepartment of Life Sciences, College of Natural Sciences, Research Institute for Natural Sciences, Hanyang University, Seoul, Republic of KoreaDepartment of Life Sciences, College of Natural Sciences, Research Institute for Natural Sciences, Hanyang University, Seoul, Republic of KoreaDepartment of Life Sciences, College of Natural Sciences, Research Institute for Natural Sciences, Hanyang University, Seoul, Republic of KoreaLaboratory Animal Medicine, College of Veterinary Medicine, Chonnam National University, Gwangju, Republic of KoreaDepartment of Biochemistry, College of Life Science and Biotechnology, Yonsei University, Seoul, Republic of KoreaDepartment of Pathology, College of Medicine, Seoul National University, Seoul, Republic of KoreaDepartment of Life Sciences, College of Natural Sciences, Research Institute for Natural Sciences, Hanyang University, Seoul, Republic of Korea; Correspondence Address correspondence to: Jae-Hoon Choi, DVM, PhD, Department of Life Sciences, College of Natural Sciences, Research Institute for Natural Sciences, Hanyang University, 222 Wangsimni-ro, Seongdong-gu, Seoul 04763, Republic of Korea. fax: (82) 2-2298-0319.Department of Veterinary Pathology, College of Veterinary Medicine, Seoul National University, Seoul, Republic of Korea; Dae-Yong Kim, DVM, PhD, Department of Veterinary Pathology, College of Veterinary Medicine, Seoul National University, 1 Gwanak-ro, Gwanak-gu, Seoul 08826, Republic of Korea. fax: (82) 2-879-2736.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.http://www.sciencedirect.com/science/article/pii/S2352345X21000783Gastric InflammationT CellImmune RegulationMucosal Metaplasia |
| spellingShingle | Du-Min Go Seung Hyun Lee Su-Hyung Lee Sang-Ho Woo Kibyeong Kim Kyeongdae Kim Kyu Seong Park Jong-Hwan Park Sang-Jun Ha Woo Ho Kim Jae-Hoon Choi Dae-Yong Kim Programmed Death Ligand 1-Expressing Classical Dendritic Cells Mitigate Helicobacter-Induced GastritisSummary Cellular and Molecular Gastroenterology and Hepatology Gastric Inflammation T Cell Immune Regulation Mucosal Metaplasia |
| title | Programmed Death Ligand 1-Expressing Classical Dendritic Cells Mitigate Helicobacter-Induced GastritisSummary |
| title_full | Programmed Death Ligand 1-Expressing Classical Dendritic Cells Mitigate Helicobacter-Induced GastritisSummary |
| title_fullStr | Programmed Death Ligand 1-Expressing Classical Dendritic Cells Mitigate Helicobacter-Induced GastritisSummary |
| title_full_unstemmed | Programmed Death Ligand 1-Expressing Classical Dendritic Cells Mitigate Helicobacter-Induced GastritisSummary |
| title_short | Programmed Death Ligand 1-Expressing Classical Dendritic Cells Mitigate Helicobacter-Induced GastritisSummary |
| title_sort | programmed death ligand 1 expressing classical dendritic cells mitigate helicobacter induced gastritissummary |
| topic | Gastric Inflammation T Cell Immune Regulation Mucosal Metaplasia |
| url | http://www.sciencedirect.com/science/article/pii/S2352345X21000783 |
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