Article Text
Abstract
Background and aims Inflammatory bowel disease (IBD) is initiated and perpetuated by a dysregulated immune response to unknown environmental antigens such as luminal bacteria in genetically susceptible hosts. SR-PSOX/CXCL16, a scavenger receptor that binds phosphatidylserine and oxidised lipoprotein, has both phagocytic activity and chemotactic properties. The aim of this study was to investigate the role of SR-PSOX/CXCL16 in patients with IBD and experimental murine colitis.
Methods The serum levels of SR-PSOX/CXCL16 were measured in patients with IBD. The roles of SR-PSOX/CXCL16 in phagocytosis of bacterial components and cytokine production by macrophages from wild-type (WT) and SR-PSOX/CXCL16 knockout (KO) mice were assessed. Colitis was induced by administering dextran sulfate sodium (DSS) to WT and SR-PSOX/CXCL16 KO mice. Colonic inflammation was analysed by clinical, histological and immunological parameters. Finally, the effect of a monoclonal antibody (mAb) to SR-PSOX/CXCL16 on DSS-induced colitis and trinitrobenzene sulfonic acid-induced colitis models was evaluated.
Results Serum levels of SR-PSOX/CXCL16 correlated significantly with the disease activity of patients with IBD. Ex vivo experiments showed that SR-PSOX/CXCL16 was involved in both phagocytosis of bacterial antigens and the T helper 1 immune response through the production of interleukin 12 and interferon γ. In vivo murine experiments demonstrated the upregulated gene expression of SR-PSOX/CXCL16 in inflamed colonic tissues and the predominant expression of SR-PSOX/CXCL16 on macrophages. SR-PSOX/CXCL16 KO mice were less susceptible to colonic inflammation than were their WT littermates. Administration of SR-PSOX/CXCL16 mAb ameliorated the condition in the two different experimental colitis models.
Conclusions SR-PSOX/CXCL16 plays a critical role in colonic inflammation and could be a potential therapeutic target for patients with IBD.
- Inflammatory bowel disease
- colonic inflammation
- macrophages
- chemokine
- SR-PSOX/CXCL16
- antibody targeted therapy
- chemokines
- inflammatory bowel disease
- macrophages
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Footnotes
Funding This work was supported by a Grant-in-Aid for Scientific Research (C) from the Ministry of Culture and Science of Japan (grant 18590677), the Kato Memorial Trust for Nambyo Research, the Shimizu Foundation for the Promotion of Immunology Research and the Japan Foundation for Applied Enzymology to HN, Grant-in-Aids for Scientific Research (16017240, 16017249, 17013051, 17659212 and 18012029) from the Ministry of Education, Culture, Sports, Science, and Technology of Japan, Grant-in-Aid for Scientific Research (15209024 and 18209027) from JSPS and Grant-in-Aid for Research on Measures for Intractable Diseases, and Research on Advanced Medical Technology (nano005) from the Ministry of Health, Labor, and Welfare, Japan to TC.
Competing interests None.
Patient consent Obtained.
Ethics approval This study was conducted with the approval of the Kyoto University Hospital Ethics Committee.
Provenance and peer review Not commissioned; externally peer reviewed.