{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,18]],"date-time":"2026-08-18T14:57:13Z","timestamp":1787065033526,"version":"build-2736575974"},"reference-count":36,"publisher":"Portland Press Ltd.","issue":"22","license":[{"start":{"date-parts":[[2021,11,3]],"date-time":"2021-11-03T00:00:00Z","timestamp":1635897600000},"content-version":"vor","delay-in-days":2,"URL":"http:\/\/creativecommons.org\/licenses\/by\/2.0\/"}],"content-domain":{"domain":["portlandpress.com"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2021,11,26]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Objective: Regulated in development and DNA damage responses-1 (REDD1) is a conserved and ubiquitous protein, which is induced in response to multiple stimuli. However, the regulation, function and clinical relevance of REDD1 in Helicobacter pylori-associated gastritis are presently unknown.<\/jats:p>\n                  <jats:p>Approach: Immunohistochemistry, real-time PCR and Western blot analyses were performed to examine the levels of REDD1 in gastric samples from H. pylori-infected patients and mice. Gastric tissues from Redd1\u2212\/\u2212 and wildtype (WT, control) mice were examined for inflammation. Gastric epithelial cells (GECs), monocytes and T cells were isolated, stimulated and\/or cultured for REDD1 regulation and functional assays.<\/jats:p>\n                  <jats:p>Results: REDD1 was increased in gastric mucosa of H. pylori-infected patients and mice. H. pylori induced GECs to express REDD1 via the phosphorylated cytotoxin associated gene A (cagA) that activated MAPKp38 pathway to mediate NF-\u03baB directly binding to REDD1 promoter. Human gastric REDD1 increased with the severity of gastritis, and mouse REDD1 from non-marrow chimera-derived cells promoted gastric inflammation that was characterized by the influx of MHCII+ monocytes. Importantly, gastric inflammation, MHCII+ monocyte infiltration, IL-23 and IL-17A were attenuated in Redd1\u2212\/\u2212 mice. Mechanistically, REDD1 in GECs regulated CXCL1 production, which attracted MHCII+ monocytes migration by CXCL1-CXCR2 axis. Then H. pylori induced MHCII+ monocytes to secrete IL-23, which favored IL-17A-producing CD4+ cell (Th17 cell) polarization, thereby contributing to the development of H. pylori-associated gastritis.<\/jats:p>\n                  <jats:p>Conclusions: The present study identifies a novel regulatory network involving REDD1, which collectively exert a pro-inflammatory effect within gastric microenvironment. Efforts to inhibit this REDD1-dependent pathway may prove valuable strategies in treating of H. pylori-associated gastritis.<\/jats:p>","DOI":"10.1042\/cs20210753","type":"journal-article","created":{"date-parts":[[2021,11,3]],"date-time":"2021-11-03T05:24:20Z","timestamp":1635917060000},"page":"2541-2558","update-policy":"https:\/\/doi.org\/10.1042\/crossmark_policy","source":"Crossref","is-referenced-by-count":14,"title":["<i>Helicobacter pylori<\/i>\n                    -induced REDD1 modulates Th17 cell responses that contribute to gastritis"],"prefix":"10.1042","volume":"135","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-7729-9798","authenticated-orcid":false,"given":"Zong-Bao","family":"Yan","sequence":"first","affiliation":[{"name":"Department of General Surgery and Center of Minimal Invasive Gastrointestinal Surgery, Southwest Hospital, Third Military Medical University, Chongqing, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jin-Yu","family":"Zhang","sequence":"additional","affiliation":[{"name":"National Engineering Research Center of Immunological Products, Department of Microbiology and Biochemical Pharmacy, College of Pharmacy and Laboratory Medicine, Third Military Medical University, Chongqing, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yi-Pin","family":"Lv","sequence":"additional","affiliation":[{"name":"Department of Digestive Diseases, General Hospital of Western Theater Command, Chengdu, Sichuan, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wen-Qing","family":"Tian","sequence":"additional","affiliation":[{"name":"Department of Endocrinology, The First Affiliated Hospital of Chongqing Medical University, Chongqing, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhi-Guo","family":"Shan","sequence":"additional","affiliation":[{"name":"Department of General Surgery and Center of Minimal Invasive Gastrointestinal Surgery, Southwest Hospital, Third Military Medical University, Chongqing, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fang-Yuan","family":"Mao","sequence":"additional","affiliation":[{"name":"National Engineering Research Center of Immunological Products, Department of Microbiology and Biochemical Pharmacy, College of Pharmacy and Laboratory Medicine, Third Military Medical University, Chongqing, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yu-Gang","family":"Liu","sequence":"additional","affiliation":[{"name":"National Engineering Research Center of Immunological Products, Department of Microbiology and Biochemical Pharmacy, College of Pharmacy and Laboratory Medicine, Third Military Medical University, Chongqing, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wan-Yan","family":"Chen","sequence":"additional","affiliation":[{"name":"National Engineering Research Center of Immunological Products, Department of Microbiology and Biochemical Pharmacy, College of Pharmacy and Laboratory Medicine, Third Military Medical University, Chongqing, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pan","family":"Wang","sequence":"additional","affiliation":[{"name":"National Engineering Research Center of Immunological Products, Department of Microbiology and Biochemical Pharmacy, College of Pharmacy and Laboratory Medicine, Third Military Medical University, Chongqing, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yun","family":"Yang","sequence":"additional","affiliation":[{"name":"National Engineering Research Center of Immunological Products, Department of Microbiology and Biochemical Pharmacy, College of Pharmacy and Laboratory Medicine, Third Military Medical University, Chongqing, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ping","family":"Cheng","sequence":"additional","affiliation":[{"name":"National Engineering Research Center of Immunological Products, Department of Microbiology and Biochemical Pharmacy, College of Pharmacy and Laboratory Medicine, Third Military Medical University, Chongqing, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Liu-Sheng","family":"Peng","sequence":"additional","affiliation":[{"name":"National Engineering Research Center of Immunological Products, Department of Microbiology and Biochemical Pharmacy, College of Pharmacy and Laboratory Medicine, Third Military Medical University, Chongqing, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ya-Ling","family":"Liao","sequence":"additional","affiliation":[{"name":"National Engineering Research Center of Immunological Products, Department of Microbiology and Biochemical Pharmacy, College of Pharmacy and Laboratory Medicine, Third Military Medical University, Chongqing, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Geng-Yu","family":"Yue","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology, The Affiliated Hospital of Zunyi Medical University, Zunyi, Guizhou, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiao-Lin","family":"Xu","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology, The Affiliated Hospital of Zunyi Medical University, Zunyi, Guizhou, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yong-Liang","family":"Zhao","sequence":"additional","affiliation":[{"name":"Department of General Surgery and Center of Minimal Invasive Gastrointestinal Surgery, Southwest Hospital, Third Military Medical University, Chongqing, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mu-Han","family":"L\u00fc","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology, Affiliated Hospital of Southwest Medical University, Luzhou, Sichuan, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7825-0032","authenticated-orcid":false,"given":"Yuan","family":"Zhuang","sequence":"additional","affiliation":[{"name":"National Engineering Research Center of Immunological Products, Department of Microbiology and Biochemical Pharmacy, College of Pharmacy and Laboratory Medicine, Third Military Medical University, Chongqing, China"},{"name":"Department of Gastroenterology, The Affiliated Hospital of Zunyi Medical University, Zunyi, Guizhou, China"},{"name":"Department of Gastroenterology, Affiliated Hospital of Southwest Medical University, Luzhou, Sichuan, China"},{"name":"Department of Gastroenterology, Southwest Hospital, Third Military Medical University, Chongqing, China"},{"name":"Jiangsu Key Laboratory of Medical Science and Laboratory Medicine, School of Medicine, Jiangsu University, Jiangsu, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"288","published-online":{"date-parts":[[2021,11,26]]},"reference":[{"key":"2021120810264307400_B1","doi-asserted-by":"publisher","first-page":"420","DOI":"10.1053\/j.gastro.2017.04.022","article-title":"Global prevalence of Helicobacter pylori infection: systematic review and meta-analysis","volume":"153","author":"Hooi","year":"2017","journal-title":"Gastroenterology"},{"key":"2021120810264307400_B2","doi-asserted-by":"publisher","first-page":"1597","DOI":"10.1056\/NEJMcp1001110","article-title":"Clinical practice. 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