Astragalus Polysaccharide Alleviates Ulcerative Colitis by Regulating the Balance of MTh17/mTreg Cells Through TIGIT/CD155 Signaling

Overview

Journal Molecules

Publisher MDPI

Specialty Biology

Date 2024 Jan 11

PMID 38202824

Authors

Qi Wan

Jiaqi Huang

Qiuping Xiao

Zeyun Zhang

Zheyan Zhang

Li Huang

Yifei Deng

Bailing Deng

Haimei Zhao

Youbao Zhong

Duanyong Liu

Affiliations

Soon will be listed here.

Abstract

The balance between memory Th17 cells (mTh17) and memory Treg cells (mTreg) plays a key role in the pathogenesis of ulcerative colitis (UC), and TIGIT signaling is involved in the differentiation of mTh17/mTreg cells. Astragalus polysaccharide (APS) has good immunomodulatory and anti-inflammatory effects. Here, the regulatory effects and potential mechanisms of APS on mTh17/mTreg cells in UC are explored. A UC model was induced with dextran sulfate sodium (DSS) and treated simultaneously with APS (200 mg/kg/day) for 10 days. After APS treatment, the mice showed a significant increase in colonic length and a significant decrease in colonic weight, colonic weight index and colonic weight/colonic length, and more intact mucosa and lighter inflammatory cell infiltration. Notably, APS significantly down-regulated the percentages of Th17 (CD4CCR6), cmTh17 (CD4CCR7CCR6) and emTh17 (CD4CCR7CCR6) cells and significantly up-regulated the percentages of cmTreg (CD4CCR7Foxp3) and emTreg (CD4CCR7Foxp3) cells in the mesenteric lymph nodes of the colitis mice. Importantly, APS reversed the expression changes in the TIGIT molecule on mTh17/mTreg cells in the colitis mice with fewer CD4CCR6TIGIT, CD4CCR7CCR6TIGIT and CD4CCR7CCR6TIGIT cells and more CD4Foxp3TIGIT, CD4CCR7Foxp3TIGIT and CD4CCR7Foxp3TIGIT cells. Meanwhile, APS significantly inhibited the protein expression of the TIGIT ligands CD155, CD113 and CD112 and downstream proteins PI3K and AKT in the colon tissues of the colitis mice. In conclusion, APS effectively alleviated DSS-induced UC in mice by regulating the balance between mTh17/mTreg cells, which was mainly achieved through regulation of the TIGIT/CD155 signaling pathway.

Citing Articles

Traditional Chinese medicine treats ulcerative colitis by regulating gut microbiota, signaling pathway and cytokine: Future novel method option for pharmacotherapy.

Wang T, Liu X, Zhang W, Wang J, Wang T, Yue W Heliyon. 2024; 10(6):e27530.

PMID: 38501018 PMC: 10945194. DOI: 10.1016/j.heliyon.2024.e27530.

References

Peters K, McDonald T, Muhammad F, Walsh M, Drenen K, Montieth A . A2Ar-dependent PD-1+ and TIGIT+ Treg cells have distinct homing requirements to suppress autoimmune uveitis in mice. Mucosal Immunol. 2023; 16(4):422-431. PMC: 10512849. DOI: 10.1016/j.mucimm.2023.04.005. View

Meng Q, Du X, Wang H, Gu H, Zhan J, Zhou Z . Astragalus polysaccharides inhibits cell growth and pro-inflammatory response in IL-1β-stimulated fibroblast-like synoviocytes by enhancement of autophagy via PI3K/AKT/mTOR inhibition. Apoptosis. 2017; 22(9):1138-1146. DOI: 10.1007/s10495-017-1387-x. View

Bsat M, Chapuy L, Rubio M, Wassef R, Richard C, Schwenter F . Differential Pathogenic Th17 Profile in Mesenteric Lymph Nodes of Crohn's Disease and Ulcerative Colitis Patients. Front Immunol. 2019; 10:1177. PMC: 6547831. DOI: 10.3389/fimmu.2019.01177. View

He H, Chen Q, Fan H, Leng X, Zhu F, Gao F . Extracellular vesicles produced by bone marrow mesenchymal stem cells overexpressing programmed death-ligand 1 ameliorate dextran sodium sulfate-induced ulcerative colitis in rats by regulating Th17/Treg cell balance through PTEN/PI3K/AKT/mTOR.... J Gastroenterol Hepatol. 2022; 37(12):2243-2254. PMC: 10087423. DOI: 10.1111/jgh.15987. View

Kryczek I, Zhao E, Liu Y, Wang Y, Vatan L, Szeliga W . Human TH17 cells are long-lived effector memory cells. Sci Transl Med. 2011; 3(104):104ra100. PMC: 3345568. DOI: 10.1126/scitranslmed.3002949. View

Zuo X, Bi L, Cao H . Astragalus polysaccharides affects multidrug resistance gene 1 and Pglycoprotein 170 in adriamycin nephropathy rats via regulating microRNA16/NFκB axis. Zhong Nan Da Xue Xue Bao Yi Xue Ban. 2022; 47(1):26-34. PMC: 10930492. DOI: 10.11817/j.issn.1672-7347.2022.201001. View

Yeo J, Ko M, Lee D, Park Y, Jin H . TIGIT/CD226 Axis Regulates Anti-Tumor Immunity. Pharmaceuticals (Basel). 2021; 14(3). PMC: 7997242. DOI: 10.3390/ph14030200. View

Fan N, Wang S, Ortiz G, Chauhan S, Chen Y, Dana R . Autoreactive memory Th17 cells are principally derived from T-betRORγt Th17/1 effectors. J Autoimmun. 2022; 129:102816. PMC: 9106930. DOI: 10.1016/j.jaut.2022.102816. View

Coletta M, Paroni M, Alvisi M, De Luca M, Rulli E, Mazza S . Immunological Variables Associated With Clinical and Endoscopic Response to Vedolizumab in Patients With Inflammatory Bowel Diseases. J Crohns Colitis. 2020; 14(9):1190-1201. DOI: 10.1093/ecco-jcc/jjaa035. View

10.

Lee G . The Balance of Th17 versus Treg Cells in Autoimmunity. Int J Mol Sci. 2018; 19(3). PMC: 5877591. DOI: 10.3390/ijms19030730. View

11.

Banta K, Xu X, Chitre A, Au-Yeung A, Takahashi C, OGorman W . Mechanistic convergence of the TIGIT and PD-1 inhibitory pathways necessitates co-blockade to optimize anti-tumor CD8 T cell responses. Immunity. 2022; 55(3):512-526.e9. PMC: 9287124. DOI: 10.1016/j.immuni.2022.02.005. View

12.

Ma C, Sedano R, Almradi A, Vande Casteele N, Parker C, Guizzetti L . An International Consensus to Standardize Integration of Histopathology in Ulcerative Colitis Clinical Trials. Gastroenterology. 2021; 160(7):2291-2302. PMC: 8851891. DOI: 10.1053/j.gastro.2021.02.035. View

13.

Devilard E, Xerri L, Dubreuil P, Lopez M, Reymond N . Nectin-3 (CD113) interacts with Nectin-2 (CD112) to promote lymphocyte transendothelial migration. PLoS One. 2013; 8(10):e77424. PMC: 3792040. DOI: 10.1371/journal.pone.0077424. View

14.

Zhao Q, Duck L, Huang F, Alexander K, Maynard C, Mannon P . CD4 T cell activation and concomitant mTOR metabolic inhibition can ablate microbiota-specific memory cells and prevent colitis. Sci Immunol. 2020; 5(54). DOI: 10.1126/sciimmunol.abc6373. View

15.

Du Y, Wan H, Huang P, Yang J, He Y . A critical review of Astragalus polysaccharides: From therapeutic mechanisms to pharmaceutics. Biomed Pharmacother. 2022; 147:112654. DOI: 10.1016/j.biopha.2022.112654. View

16.

Li Z, Sun Q, Liu Q, Mu X, Wang H, Zhang H . Compound 511 ameliorates MRSA-induced lung injury by attenuating morphine-induced immunosuppression in mice via PI3K/AKT/mTOR pathway. Phytomedicine. 2022; 108:154475. DOI: 10.1016/j.phymed.2022.154475. View

17.

Zhong Y, Xiao Q, Kang Z, Huang J, Ge W, Wan Q . Astragalus polysaccharide alleviates ulcerative colitis by regulating the balance of Tfh/Treg cells. Int Immunopharmacol. 2022; 111:109108. DOI: 10.1016/j.intimp.2022.109108. View

18.

Abreu M, Davies J, Quintero M, Delmas A, Diaz S, Martinez C . Transcriptional Behavior of Regulatory T Cells Predicts IBD Patient Responses to Vedolizumab Therapy. Inflamm Bowel Dis. 2022; 28(12):1800-1812. PMC: 9713523. DOI: 10.1093/ibd/izac151. View

19.

Wu J, Li C, Bai L, Wu J, Bo R, Ye M . Structural differences of polysaccharides from Astragalus before and after honey processing and their effects on colitis mice. Int J Biol Macromol. 2021; 182:815-824. DOI: 10.1016/j.ijbiomac.2021.04.055. View

20.

Liu S, Zhang H, Li M, Hu D, Li C, Ge B . Recruitment of Grb2 and SHIP1 by the ITT-like motif of TIGIT suppresses granule polarization and cytotoxicity of NK cells. Cell Death Differ. 2012; 20(3):456-64. PMC: 3569986. DOI: 10.1038/cdd.2012.141. View