首页|Tubulointerstitial nephritis antigen-like 1 is a novel matricellular protein that promotes gastric bacterial colonization and gastritis in the setting of Helicobacter pylori infection

Tubulointerstitial nephritis antigen-like 1 is a novel matricellular protein that promotes gastric bacterial colonization and gastritis in the setting of Helicobacter pylori infection

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The interaction between the gastric epithelium and immune cells plays key roles in H.pylori-associated pathology.Here,we demonstrate a procolonization and proinflammatory role of tubulointerstitial nephritis antigen-like 1(TINAGL1),a newly discovered matricellular protein,in H.pylori infection.Increased TINAGL1 production by gastric epithelial cells(GECs)in the infected gastric mucosa was synergistically induced by H.pylori and IL-1β via the ERK-SP1 pathway in a cagA-dependent manner.Elevated human gastric TINAGL1 correlated with H.pylori colonization and the severity of gastritis,and mouse TINAGL1 derived from non-bone marrow-derived cells promoted bacterial colonization and inflammation.Importantly,H.pylori colonization and inflammation were attenuated in Tinagl1-/-and Tinagl1ΔGEC mice and were increased in mice injected with mouse TINAGL1.Mechanistically,TINAGL1 suppressed CCL21 expression and promoted CCL2 production in GECs by directly binding to integrin α5β1 to inhibit ERK and activate the NF-κB pathway,respectively,which not only led to decreased gastric influx of moDCs via CCL21-CCR7-dependent migration and,as a direct consequence,reduced the bacterial clearance capacity of the H.pylori-specific Th1 response,thereby promoting H.pylori colonization,but also resulted in increased gastric influx of Ly6Chigh monocytes via CCL2-CCR2-dependent migration.In turn,TINAGL1 induced the production of the proinflammatory protein S100A11 by Ly6Chigh monocytes,promoting H.pylori-associated gastritis.In summary,we identified a model in which TINAGL1 collectively ensures H.pylori persistence and promotes gastritis.

Helicobacter pyloriTINAGL1ColonizationGastritis

Yongsheng Teng、Rui Xie、Jingyu Xu、Pan Wang、Wanyan Chen、Zhiguo Shan、Zongbao Yan、Fangyuan Mao、Ping Cheng、Liusheng Peng、Jinyu Zhang、Wenqing Tian、Shiming Yang、Yongliang Zhao、Weisan Chen、Quanming Zou、Yuan Zhuang

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Department of Microbiology and Biochemical Pharmacy,College of Pharmacy and Laboratory Medicine,Third Military Medical University,Chongqing,China

The 940th Hospital of Joint Logistics Support Force of PLA,Lanzhou,China

The Collaborative Innovation Center of Tissue Damage Repair and Regeneration Medicine of Zunyi Medical University,Zunyi,Guizhou,China

Department of General Surgery and Center of Minimal Invasive Gastrointestinal Surgery,Southwest Hospital,Third Military Medical University,Chongqing,China

Department of Gastroenterology,Chongqing University Cancer Hospital,Chongqing,China

Department of Gastroenterology,XinQiao Hospital,Third Military Medical University,Chongqing,China

La Trobe Institute of Molecular Science,La Trobe University,Bundoora,VIC,Australia

Department of Gastroenterology,Affiliated Hospital of Southwest Medical University,Luzhou,Sichuan,China

National Engineering Research Center of Immunological Products,Third Military Medical University,Chongqing,China

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National Natural Science Foundation of ChinaNational Natural Science Foundation of ChinaNational Natural Science Foundation of ChinaNational Natural Science Foundation of ChinaChongqing Natural Science Fund for Distinguished Young ScholarsScience Innovation Capacity Promotion Project of Army Medical UniversityNational Key Research and Development Program of ChinaCollaborative Innovation Center of Chinese Ministry of Education

82070578818703948200053081670510cstc2019jcyjjqX00032019XQY032016YFC13022002020-39

2023

10.1038/s41423-023-01055-4

中国免疫学杂志(英文版)
中国免疫学会

中国免疫学杂志(英文版)

CSTPCDCSCDSCI
影响因子：0.731
ISSN：1672-7681
年,卷(期)：2023.20(8)
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