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

doi:10.1038/s41598-018-20957-2

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

School of Medicine

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8 Scopus citations

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 language	English (US)
Article number	3821
Journal	Scientific reports
Volume	8
Issue number	1
DOIs	https://doi.org/10.1038/s41598-018-20957-2
State	Published - Dec 1 2018

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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

@article{64120907b34b475e80b6a7d2582998e4,

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

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.",

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

note = "Funding Information: We acknowledge the support of the Center for Resources, Research and Development of Kaohsiung Medical University for use of the confocal laser scanning microscope. Supports of this study were by grants from the Academia Sinica (AS-102-TP2-B02, AS-105-TP-B05) and partially by Kaohsiung Medical University “Aim for the Top Universities Grant” and “The Talent Plan” (KMU-TP103E16, KMU-TP104E21, KMU-TP104G00, KMU-TP105A04 and KMU-SH000184) and Kaohsiung Medical University “Global Net working Talent Plan” (105KMUOR04). Publisher Copyright: {\textcopyright} 2018 The Author(s).",

year = "2018",

month = dec,

day = "1",

doi = "10.1038/s41598-018-20957-2",

language = "English (US)",

volume = "8",

journal = "Scientific reports",

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T1 - Stromal C-type lectin receptor COLEC12 integrates H. pylori, PGE2-EP2/4 axis and innate immunity in gastric diseases

AU - Chang, Lin Li

AU - Hsu, Wen Hung

AU - Kao, Mou Chieh

AU - Chou, Chih Chung

AU - Lin, Chung Cheng

AU - Liu, Chung Jung

AU - Weng, Bi Chuang

AU - Kuo, Fu Chen

AU - Kuo, Chao Hung

AU - Lin, Ming Hong

AU - Wang, Chun Jen

AU - Lin, Chun Hung

AU - Wu, Deng Chyang

AU - Huang, Shau Ku

N1 - Funding Information: We acknowledge the support of the Center for Resources, Research and Development of Kaohsiung Medical University for use of the confocal laser scanning microscope. Supports of this study were by grants from the Academia Sinica (AS-102-TP2-B02, AS-105-TP-B05) and partially by Kaohsiung Medical University “Aim for the Top Universities Grant” and “The Talent Plan” (KMU-TP103E16, KMU-TP104E21, KMU-TP104G00, KMU-TP105A04 and KMU-SH000184) and Kaohsiung Medical University “Global Net working Talent Plan” (105KMUOR04). Publisher Copyright: © 2018 The Author(s).

PY - 2018/12/1

Y1 - 2018/12/1

N2 - 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.

AB - 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.

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

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