文献类型：期刊文献

英文题名：atRA Attenuates High Salt-Driven EAE Mainly Through Suppressing Th17-Like Regulatory T Cell Response Mediated by the Inhibition of IL-23R Signaling Pathway

作者：Tian, Jiale[1];Li, Yating[1];Gao, Shuo[1,3];Wang, Yong[1];Li, Haolin[2];Wei, Xiaofeng[3,6];Yang, Jun[1];Gu, Youquan[4];Wang, Haidong[2];Luo, Yang[1,3,4,5]

第一作者：Tian, Jiale

通信作者：Luo, Y[1];Luo, Y[2];Luo, Y[3];Luo, Y[4]

机构：[1]Lanzhou Univ, Clin Med Coll 1, Lanzhou 730000, Gansu, Peoples R China;[2]Gansu Univ Chinese Med, Gansu Hosp Tradit Chinese Med, Rheumat Bone Dis Ctr, Lanzhou 730000, Gansu, Peoples R China;[3]Key Lab Biotherapy & Regenerat Med, Lanzhou 730000, Gansu, Peoples R China;[4]Lanzhou Univ, Hosp 1, Dept Neurol, Lanzhou 730000, Gansu, Peoples R China;[5]Penn State Coll Med, Dept Med, Div Rheumatol, Hershey, PA 17033 USA;[6]Clin Res Ctr Gen Surg Gansu Prov, Lanzhou 730000, Gansu, 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, Lanzhou 730000, Gansu, Peoples R China;[4]corresponding author), Penn State Coll Med, Dept Med, Div Rheumatol, Hershey, PA 17033 USA.

年份：2024

外文期刊名：INFLAMMATION

收录：;Scopus(收录号：2-s2.0-85201601088);WOS:【SCI-EXPANDED(收录号:WOS:001295748000001)】；

基金：This work was supported by the National Natural Science Foundation of China (81960293); the Natural Science Foundation of Gansu Province (20JR5RA3); the Joint Research Fund of Gansu Province (23JRRA1495), 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). DAS:No datasets were generated or analysed during the current study.

语种：英文

外文关键词：All-trans retinoid acid (atRA); Regulatory T cells (Treg cells); Experimental autoimmune encephalomyelitis (EAE); Interleukin-23 receptor (IL-23R); Th17 cells; Dendritic cells; Serum- and glucocorticoid-regulated kinase 1-dependent (SGK1)

摘要：High salt diet (HSD) is implicated in numerous disorders, which boosts Th17 cell development and weakens immunosuppressive function of regulatory T cells (Treg cells) Treg cells, leading to the exacerbation of EAE. However, little is known regarding the harness of excessive proinflammatory responses evoked by HSD. Here we show that atRA, a key vitamin A metabolite with multifaceted immunoregulatory properties has the potential in inhibiting the proinflammatory reaction of high salt. Treatment with atRA in vivo elicited the Treg generation in cervical and axillary lymph nodes (CALs), and in CNS of experimental autoimmune encephalomyelitis (EAE). Meanwhile, the proportion of Th17-like Treg cells (ROR gamma t-positive or GM-CSF-positive Treg cells) decreased in CALs. atRA also inhibited IL-17A expression in CD4(+) effector T cells. In-vitro mechanistic studies showed that atRA inhibit IL-23R but not SGK1 expression in Treg cells and this results in maintained immunosuppressive function of Treg cells even in the presence of IL-6 and high salt. Furthermore, treatment of EAE with anti-IL-23R mAb attenuated HSD-provoked EAE progress. This was associated with a reduction in the number of CNS-infiltrating Th17 cells and an increase of CAL-Treg cells. Mechanically, treatment with atRA significantly promoted LP-CD103(+)CD11c(+) dendritic cells, a subgroup of cells most closely involved in endogenous retinoic acid metabolism, and enhanced intestinal Aldh1a1 and Rdh10 expression from HSD-fed EAE mice. Interestingly, anti-IL-23R mAb administration also reduced IL-23R expression in Treg cells, along with the increased proportion of LP-CD103(+)CD11c(+) dendritic cells and Rdh10 mRNA expression. In conclusion, administration of atRA might be a way to combat the proinflammatory effects of HSD. Meanwhile, systematic inhibition of IL-23R also had a moderate therapeutic potential in inhibiting inflammatory effects of high salt, which may serve as a basis for the identification of novel therapeutic strategies against HSD-driven autoimmune disorders.