α-Methyl-Tryptophan Inhibits SLC6A14 Expression and Exhibits Immunomodulatory Effects in Crohn’s Disease

Abstract

YongCheng Su,1,* Jiangquan Li,1,* Yijia Chen,2,* Jiachen Bao,2 Ziyu Lei,1 Miaomiao Ma,1 Wenqing Zhang,1 Qian Liu,3 Beibei Xu,4 Tianhui Hu,1,3 Yiqun Hu2 1Xiamen Key Laboratory for Tumor Metastasis, Cancer Research Center, School of Medicine, Xiamen University, Xiamen, Fujian, 361102, People’s Republic of China; 2Department of Gastroenterology, The National Key Clinical Specialty, Zhongshan Hospital of Xiamen University, School of Medicine, Xiamen University, Xiamen, Fujian, 361004, People’s Republic of China; 3Integrated Chinese and Western Medicine Institute for Children Health & Drug Innovation, Jiangxi University of Chinese Medicine, Nanchang, Jiangxi, 330004, People’s Republic of China; 4Institute of Synthetic Biology, Shenzhen Institute of Advanced Technology, Chinese Academy of Sciences, Shenzhen, Guangdong, 518055, People’s Republic of China*These authors contributed equally to this workCorrespondence: Tianhui Hu, Xiamen Key Laboratory for Tumor Metastasis, Cancer Research Center, School of Medicine, Xiamen University, Xiamen, Fujian, 361102, People’s Republic of China, Email [email protected] Yiqun Hu, Department of Gastroenterology, The National Key Clinical Specialty, Zhongshan Hospital of Xiamen University, School of Medicine, Xiamen University, Xiamen, Fujian, 361004, People’s Republic of China, Email [email protected]: Crohn’s disease (CD) is a chronic inflammatory condition of the intestines with a rising global incidence. Traditional diagnostic and therapeutic methods have limitations, necessitating the exploration of more effective strategies.Methods: In this study, we employed the Gene Expression Omnibus database to identify genes that are differentially expressed in CD. RT-PCR and immunohistochemical analysis were used to SLC6A14 RNA and protein expression in the colons of CD mice and CD tissues from patients. The mouse model of CD was induced by dextran sodium sulfate (DSS). Infiltrating immune cells in mouse model were screened by flow cytometry.Results: We discovered that SLC6A14 is significantly overexpressed in CD samples, and its expression is positively correlated with the degree of infiltration by CD4+ and CD8+ T cells. The elevated levels of SLC6A14 RNA and protein were confirmed in clinical CD tissues. The SLC6A14 inhibitor α-methyl-tryptophan (α-MT) significantly decreased the expression of SLC6A14 RNA and protein in the colons of CD mice. The α-MT treatment group also exhibited reduced levels of cytokines involved in T cell differentiation (IFN-γ and TNF-α) and the expression of immune cell surface markers CXCR-3 and LAG-3. Flow cytometry analysis revealed a significant increase in the infiltration of CD4+ and CD8+ T cells in the DSS-treated group compared to the control group. Conversely, the α-MT treatment group showed a significant reduction in CD4+ and CD8+ T cell infiltration and the restoration of intestinal parameters in CD mice. These findings underscore the role of SLC6A14 in regulating intestinal immune cell infiltration during CD progression.Discussion: Our findings suggest that SLC6A14 could serve as a potential diagnostic biomarker and therapeutic target for CD. Furthermore, α-MT offers a novel approach for the clinical diagnosis and treatment of CD by targeting SLC6A14 for therapeutic intervention. Keywords: Crohn’s disease, immunosuppressant, α-MT

Keywords

• crohn's disease
• immunosuppressant
• α-mt