文献类型：期刊文献

英文题名：Itreg cells Ameliorates MOG-induced brain inflammation via endowing DC tolerogenic capacity predominantly via TGF-beta signaling mediated AKT/mTOR pathway inhibition

作者：Luo, Yang[1,2,3,4,5];Li, Yating[1];Tian, Jiale[1];Li, Haolin[6];Wang, Yong[1];Wei, Xiaofeng[2];Zhang, Long[7];Brand, David[8];Zheng, Songguo[5,9]

第一作者：Luo, Yang

通信作者：Luo, Y[1];Luo, Y[2];Luo, Y[3];Luo, Y[4];Luo, Y[5];Zheng, SG[5];Zheng, SG[6]

机构：[1]Lanzhou Univ, Clin Med Coll 1, Lanzhou 730000, Gansu, Peoples R China;[2]Key Lab Biotherapy & Regenerat Med, Lanzhou 730000, Gansu, Peoples R China;[3]Lanzhou Univ, Hosp 1, Dept Neurol, 1 Donggang West Rd, Lanzhou 730000, Gansu, Peoples R China;[4]Penn State Coll Med, Dept Med, Div Rheumatol, Hershey, PA 17033 USA;[5]Shanghai Jiao Tong Univ, Sch Cell & Gene Therapy, Dept Immunol, Shanghai 201600, Peoples R China;[6]Gansu Univ Chinese Med, Gansu Hosp Tradit Chinese Med, Rheumat Bone Dis Ctr, Lanzhou 730000, Gansu, Peoples R China;[7]Lanzhou Univ, Affiliated Hosp 2, Dept Obstet & Gynecol, Lanzhou 730000, Gansu, Peoples R China;[8]Lt Col Luke Weathers, Jr VA Med Ctr, Res Serv, Memphis, TN 38104 USA;[9]Shanghai Jiao Tong Univ, Shanghai Jiaotong Univ Sch Med, Songjiang Res Inst, Sch Cell & Gene Therapy,Dept Immunol, 227 Chongqing South Rd, Shanghai 200025, Peoples R China

第一机构：Lanzhou Univ, Clin Med Coll 1, Lanzhou 730000, Gansu, Peoples R China

通信机构：[1]corresponding author), Lanzhou Univ, Clin Med Coll 1, Lanzhou 730000, Gansu, Peoples R China;[2]corresponding author), Key Lab Biotherapy & Regenerat Med, Lanzhou 730000, Gansu, Peoples R China;[3]corresponding author), Lanzhou Univ, Hosp 1, Dept Neurol, 1 Donggang West Rd, Lanzhou 730000, Gansu, Peoples R China;[4]corresponding author), Penn State Coll Med, Dept Med, Div Rheumatol, Hershey, PA 17033 USA;[5]corresponding author), Shanghai Jiao Tong Univ, Sch Cell & Gene Therapy, Dept Immunol, Shanghai 201600, Peoples R China;[6]corresponding author), Shanghai Jiao Tong Univ, Shanghai Jiaotong Univ Sch Med, Songjiang Res Inst, Sch Cell & Gene Therapy,Dept Immunol, 227 Chongqing South Rd, Shanghai 200025, Peoples R China.

年份：2025

卷号：32

期号：1

外文期刊名：MOLECULAR MEDICINE

收录：;WOS:【SCI-EXPANDED(收录号:WOS:001662301700001)】；

基金：The National Natural Science Foundation of China (81960293, 81871224, 82371817); the Natural Science Foundation of Gansu Province (20JR5RA3); the Joint Research Fund of Gansu Province (23JRRA1495), and the China Postdoctoral Foundation project (2023M731460). the Lanzhou Chengguan District talent innovation and entrepreneurship project (2023RCCX0021), the Hui-Chun Chin and Tsung-Dao Lee Chinese Undergraduate Research Endowment (LZU-JZH2634) and the First Hospital of Lanzhou University excellent doctoral research start-up fund (ldyyyn2018-23).

语种：英文

外文关键词：Experimental autoimmune encephalomyelitis (EAE); High salt diet; IL-10; Induced regulatory T cells (iTregs); TGF-beta; Thymus-derived natural regulatory T cells (tTregs); Tolerogenic DCs (tDCs)

摘要：BackgroundCertain environmental factors have been known to compromise the suppressive capacity of thymus-derived regulatory T cells (tTregs) while leaving transforming growth factor-beta (TGF-beta)-induced Tregs (iTregs) unaffected. The objective of this study is to ascertain whether both Treg subsets exhibit comparable efficacy in regulating brain inflammation through the inhibition of immunogenic dendritic cells (DCs) and instead induce tolerogenic DCs.ObjectivesWe aimed to delineate the different therapeutic potential roles of both Treg subsets in promoting the tolerogenic capacity of DCs and elucidate the mechanistic crosstalk between Tregs and DCs.MethodsThe clinical scores of experimental autoimmune encephalomyelitis (EAE) mice were continuously monitored, brain inflammation was assessed through hematoxylin and eosin (H&E) staining, and the presence of brain-infiltrating Th1/Th17 cells as well as splenic CD11c+ DCs was analyzed using flow cytometry. Additionally, a DC-T coculture assay was conducted, and the underlying mechanisms were determined by western blotting and flow cytometry.ResultsiTregs exhibit greater efficacy than tTregs in mitigating brain inflammation in both EAE and EAE provoked by a high-salt diet. iTregs suppress the pro-inflammatory activity of DCs while promoting the generation of a tolerance-inducing DC phenotype. This effect is primarily mediated by membrane-bound TGF-beta signaling, rather than through IL-10R signaling, and involves the inhibition of the AKT/mTOR pathway.ConclusioniTreg cells play a pivotal role in orchestrating the formation of a robust immunoregulatory circuit involving tolerogenic DCs, which holds significant promise as a target for the development of innovative immunotherapeutic strategies for autoimmune disorders.