Abstract

Tissue stroma is known to be important in regulating Hp-mediated inflammation, but its interaction with Hp and dendritic cells (DCs) remains to be determined. To this end, the potential crosstalk between H. pylori (Hp) infected gastric stromal cells (Hp-GSCs) and DCs was investigated. Primary GSCs from cancerous and adjacent normal tissues were generated from gastric cancer patients, and monocyte-derived DCs were obtained from healthy individuals. Levels of cytokines and prostaglandin E2 (PGE2) were measured by ELISA, and C-type lectin expression in GSCs was assessed by flow cytometry and immunohistochemistry. In a trans-well co-culture system, significantly upregulated DC-derived IL-23 expression was found when DCs were co-cultured with Hp-infected GSCs (Hp-GSCs). Further, PGE2 from Hp-GSCs was discovered to possess the priming effect, which could be inhibited by anti-COLEC12 (Collectin subfamily member 12) Abs, COLEC12 knockdown or when alpha3-fucosyltransferase-null (futB; HP0651) strain of Hp was used. Also, the expression of COLEC12 was co-localized with CD90+ stromal cells in cancerous tissues. Hp-GSCs-conditioned DCs were able to induce the expression of IL-17 from CD4+ T cells, which could be inhibited by IL-23-neutralizing Abs. These results suggested the importance of COLEC12 as a receptor involved in Hp-stromal cell interaction and its subsequent conditioning effect on DCs.

Details

Title
Stromal C-type lectin receptor COLEC12 integrates H. pylori, PGE2-EP2/4 axis and innate immunity in gastric diseases
Author
Lin-Li, Chang 1 ; Wen-Hung, Hsu 2 ; Kao, Mou-Chieh 3 ; Chih-Chung Chou 4 ; Chung-Cheng, Lin 5 ; Chung-Jung, Liu 6 ; Bi-Chuang Weng 6 ; Fu-Chen, Kuo 7 ; Chao-Hung, Kuo 8 ; Ming-Hong, Lin 4 ; Wang, Chun-Jen 9 ; Chun-Hung, Lin 10 ; Wu, Deng-Chyang 11 ; Huang, Shau-Ku 12 

 Department of Microbiology and Immunology, Faculty of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan; Graduate Institute of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan; Graduate Institute of Clinical Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan; Center for Infectious Disease and Cancer Research, Kaohsiung Medical University, Kaohsiung, Taiwan; Department of Medical Research, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan 
 Graduate Institute of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan; Division of Gastroenterology, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan 
 Institute of Molecular Medicine, National Tsing Hua University, Hsinchu, Taiwan; Department of Life Science, National Tsing Hua University, Hsinchu, Taiwan 
 Department of Microbiology and Immunology, Faculty of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan 
 Graduate Institute of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan 
 Division of Gastroenterology, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan 
 School of Medicine, College of Medicine, E-Da Hospital, I-Shou University, Kaohsiung, Taiwan 
 Graduate Institute of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan; Division of Gastroenterology, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan; Center for Stem Cell Research, Kaohsiung Medical University, Kaohsiung, Taiwan 
 Institute of Molecular Medicine, National Tsing Hua University, Hsinchu, Taiwan 
10  Chemical Biology and Molecular Biophysics, Taiwan International Graduate Program and the Institute of Biological Chemistry, Academia Sinica, Taipei, Taiwan; Institute of Biochemical Sciences, National Taiwan University, Taipei, Taiwan; Department of Chemistry, National Taiwan University, Taipei, Taiwan 
11  Graduate Institute of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan; Center for Infectious Disease and Cancer Research, Kaohsiung Medical University, Kaohsiung, Taiwan; Division of Gastroenterology, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan; Center for Stem Cell Research, Kaohsiung Medical University, Kaohsiung, Taiwan; Department of Internal Medicine, Kaohsiung Municipal Ta-Tung Hospital, Kaohsiung, Taiwan 
12  National Institute of Environmental Health Sciences, National Health Research Institutes, Miaoli, Taiwan; Research Center for Environmental Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan; Shen-Zhen University Lo-Hu Hospital, Shen-Zhen, China; Johns Hopkins Asthma and Allergy Center, School of Medicine, Johns Hopkins University, Baltimore, Maryland, USA 
Pages
1-10
Publication year
2018
Publication date
Feb 2018
Publisher
Nature Publishing Group
e-ISSN
20452322
Source type
Scholarly Journal
Language of publication
English
ProQuest document ID
2009221984
Copyright
© 2018. This work is published under http://creativecommons.org/licenses/by/4.0/ (the “License”). Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.