Stromal C-type lectin receptor COLEC12 integrates H. pylori, PGE2-EP2/4 axis and innate immunity in gastric diseases

Lin Li Chang, Wen Hung Hsu, Mou Chieh Kao, Chih Chung Chou, Chung Cheng Lin, Chung Jung Liu, Bi Chuang Weng, Fu Chen Kuo, Chao Hung Kuo, Ming Hong Lin, Chun Jen Wang, Chun Hung Lin, Deng Chyang Wu, Shau Ku Huang

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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.

Original languageEnglish
Article number3821
JournalScientific Reports
Volume8
Issue number1
DOIs
Publication statusPublished - Dec 1 2018
Externally publishedYes

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    Chang, L. L., Hsu, W. H., Kao, M. C., Chou, C. C., Lin, C. C., Liu, C. J., Weng, B. C., Kuo, F. C., Kuo, C. H., Lin, M. H., Wang, C. J., Lin, C. H., Wu, D. C., & Huang, S. K. (2018). Stromal C-type lectin receptor COLEC12 integrates H. pylori, PGE2-EP2/4 axis and innate immunity in gastric diseases. Scientific Reports, 8(1), [3821]. https://doi.org/10.1038/s41598-018-20957-2