{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,22]],"date-time":"2026-07-22T15:43:52Z","timestamp":1784735032862,"version":"3.55.0"},"reference-count":35,"publisher":"American Society for Clinical Investigation","issue":"9","license":[{"start":{"date-parts":[[2026,5,1]],"date-time":"2026-05-01T00:00:00Z","timestamp":1777593600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"crossref","award":["82470595"],"award-info":[{"award-number":["82470595"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"crossref","award":["82070578"],"award-info":[{"award-number":["82070578"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"crossref"}]},{"name":"Chongqing Natural Science Fund for Distinguished Young Scholars","award":["cstc2019jcyjjqX0003"],"award-info":[{"award-number":["cstc2019jcyjjqX0003"]}]},{"name":"Collaborative Innovation Center of Chinese Ministry of Education","award":["2020-39"],"award-info":[{"award-number":["2020-39"]}]},{"name":"Grant of Sichuan Science and Technology Program","award":["2024NSFSC1684"],"award-info":[{"award-number":["2024NSFSC1684"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2026,5,1]]},"abstract":"<jats:p>\n                    Bacteria-modulated gastric epithelial cells (GECs) play key roles in\n                    <jats:italic>Helicobacter pylori<\/jats:italic>\n                    \u2013associated pathology. Here, we demonstrate both procolonization and proinflammation roles of GEC-derived PPFIA4 in\n                    <jats:italic>H<\/jats:italic>\n                    .\n                    <jats:italic>pylori<\/jats:italic>\n                    infection. PPFIA4 was elevated in GECs from gastric mucosa of\n                    <jats:italic>H<\/jats:italic>\n                    .\n                    <jats:italic>pylori<\/jats:italic>\n                    \u2013infected patients and mice. PPFIA4 could be synergistically induced by\n                    <jats:italic>H<\/jats:italic>\n                    .\n                    <jats:italic>pylori<\/jats:italic>\n                    and IL-33 via the CagA\/AP1 pathway. Human gastric PPFIA4 correlated with\n                    <jats:italic>H<\/jats:italic>\n                    .\n                    <jats:italic>pylori<\/jats:italic>\n                    colonization and the severity of gastritis, and\n                    <jats:italic>H<\/jats:italic>\n                    .\n                    <jats:italic>pylori<\/jats:italic>\n                    colonization and inflammation were attenuated in\n                    <jats:italic>Ppfia4<\/jats:italic>\n                    <jats:sup>\u0394GEC<\/jats:sup>\n                    mice. Mechanistically, PPFIA4\u2019s SAM1 domain bound domains from CaMK to the first L27 of CASK and subsequently formed a PPFIA4\/CASK\/AKT1 complex to activate AKT1, resulting in NF-\u03baB activation and MMP1\/CXCL3 secretion. This not only led to decreased E-cadherin and ZO-1 by MMP1, thereby promoting gastric mucosal damage to foster\n                    <jats:italic>H<\/jats:italic>\n                    .\n                    <jats:italic>pylori<\/jats:italic>\n                    colonization, but also resulted in increased gastric influx of G-MDSCs via CXCL3-dependent migration, thereby promoting gastritis and impairing\n                    <jats:italic>H<\/jats:italic>\n                    .\n                    <jats:italic>pylori<\/jats:italic>\n                    \u2013specific IFN-\u03b3\u2013producing CD4\n                    <jats:sup>+<\/jats:sup>\n                    T cell responses to foster\n                    <jats:italic>H<\/jats:italic>\n                    .\n                    <jats:italic>pylori<\/jats:italic>\n                    colonization. Furthermore, we identified a PPFIA4 inhibitor, kira6, which effectively inhibited GEC\u2019s MMP1\/CXCL3 production and ameliorated gastric\n                    <jats:italic>H<\/jats:italic>\n                    .\n                    <jats:italic>pylori<\/jats:italic>\n                    colonization and gastritis. Overall, PPFIA4 could be a promising therapeutic target, as it collectively ensures\n                    <jats:italic>H<\/jats:italic>\n                    .\n                    <jats:italic>pylori<\/jats:italic>\n                    persistence and promotes gastritis.\n                  <\/jats:p>","DOI":"10.1172\/jci193848","type":"journal-article","created":{"date-parts":[[2026,4,30]],"date-time":"2026-04-30T18:00:58Z","timestamp":1777572058000},"source":"Crossref","is-referenced-by-count":1,"title":["Helicobacter pylori\u2013induced PPFIA4 orchestrates immune network\u2013promoting gastritis and gastric bacterial colonization"],"prefix":"10.1172","volume":"136","author":[{"given":"Pan","family":"Wang","sequence":"first","affiliation":[{"name":"Department of Gastroenterology, The 940 Hospital of Joint Logistic Support Force of PLA, Lanzhou, China."},{"name":"Collaborative Innovation Center of Tissue Damage Repair and Regeneration Medicine, Zunyi Medical University, Zunyi, China."},{"name":"National Engineering Research Center of Immunological Products, Department of Microbiology and Biochemical Pharmacy, College of Pharmacy and Laboratory Medicine, and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nan","family":"You","sequence":"additional","affiliation":[{"name":"Department of Hepatobiliary Surgery, XinQiao Hospital, Third Military Medical University, Chongqing, China."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yong-Sheng","family":"Teng","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology, Chongqing General Hospital, Chongqing University, Chongqing, China."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yi-Pin","family":"Lv","sequence":"additional","affiliation":[{"name":"Department of Infectious Disease, The\u2000General Hospital of Western\u2000Theater Command, Chengdu, China."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wen-Qing","family":"Tian","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology, Chongqing University Cancer Hospital, Chongqing, China."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jing-Yu","family":"Xu","sequence":"additional","affiliation":[{"name":"Collaborative Innovation Center of Tissue Damage Repair and Regeneration Medicine, Zunyi Medical University, Zunyi, China."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rui","family":"Xie","sequence":"additional","affiliation":[{"name":"Department of Endoscopy and Digestive System, Guizhou Provincial People\u2019s Hospital, Guiyang, China."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jiang-Bo","family":"Wu","sequence":"additional","affiliation":[{"name":"Collaborative Innovation Center of Tissue Damage Repair and Regeneration Medicine, Zunyi Medical University, Zunyi, 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Products, Department of Microbiology and Biochemical Pharmacy, College of Pharmacy and Laboratory Medicine, and"}],"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, and"}],"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, and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shou-Lu","family":"Luo","sequence":"additional","affiliation":[{"name":"National Engineering Research Center of Immunological Products, Department of Microbiology and Biochemical Pharmacy, College of Pharmacy and 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