间充质干细胞外泌体对牙周炎中辅助性T细胞的调控作用  

Regulation of mesenchymal stem cell-derived exosomes on helper T cells in periodontitis

作　　者：温雨琪 郭淑娟[1] 丁一[1] WEN Yuqi;GUO Shujuan;DING Yi(State Key Laboratory of Oral Diseases&National Center for Stomatology&National Clinical Research Center for Oral Diseases&Frontier Innovation Center for Dental Medcine Plus&Department of Periodontics,West China Hospital of Stomatology,Sichuan University,Chengdu 610041,China)

机构地区：[1]口腔疾病防治全国重点实验室国家口腔医学中心国家口腔疾病临床医学研究中心口腔医学+前沿医学创新中心四川大学华西口腔医院牙周科,四川成都610041

出　　处：《口腔疾病防治》2025年第5期409-416,共8页Journal of Prevention and Treatment for Stomatological Diseases

基　　金：国家自然科学基金项目(82071121)。

摘　　要：辅助性T细胞(T helper cells,Th细胞)在牙周炎的发病机制中具有重要作用。在牙周炎的发生发展中,Th1细胞与Th17细胞及其分泌的致炎性细胞因子INF-γ、IL-17等水平上升,Th2细胞与调节性T细胞(regu-latory T Cells,Tregs)及其产生的抑炎性细胞因子IL-4、TGF-β等水平降低。通过间充质干细胞(mesenchymal stem cells,MSCs)或其外泌体(exosomes,Exos)对牙周炎施加干预时,能够改变辅助性T细胞及相应细胞因子的变化趋势,从而减少牙周炎骨丧失或促进骨再生。间充质干细胞外泌体(mesenchymal stem cell-derived exo-somes,MSC-exos)能够通过携带的蛋白分子及微RNAs直接调控辅助性T细胞。当前研究中发现MSC-exos可携带具有免疫抑制作用的蛋白分子:细胞程序性死亡配体1(programmed cell death 1-ligand,PD-L1)与吲哚胺-2,3-双加氧酶分子可调控Th17-Treg平衡;转化生长因子-β(transforming growth factorβ,TGF-β)抑制T淋巴细胞增殖并通过维持叉头框P3(forkhead box protein O3,FOXP3)和Smad的表达促进Tregs分化;CD73则催化单磷酸腺苷分解产生腺苷,与Th1细胞内的腺苷2A受体结合,促使Th1细胞自身凋亡。MiRNA同样具有免疫调控能力:牙周膜干细胞外泌体携带的miRNA-155-5p通过靶向sirtuin-1而降低Th17细胞的分化,其携带的miR-205-5p能够靶向XBP1,进而恢复大鼠牙周炎局部的Th17-Treg平衡。牙髓干细胞外泌体通过miR-1246/Nfat5轴恢复Th17-Treg平衡;骨髓间充质干细胞外泌体携带的miR-1246靶向ACE2,使共培养的CD4阳性T淋巴细胞向Tregs分化。此外,MSC-exos也可以通过抗原呈递细胞或巨噬细胞等其他免疫细胞而间接促进Tregs的分化。本文主要针对辅助性T细胞在牙周炎中的变化及作用,以及间充质干细胞外泌体对辅助性T细胞的调控作用做一综述,希望为牙周炎的免疫治疗提供新思路。T helper cells(Th cells)play an important role in periodontitis.During the progression of periodontitis,the levels of pro-inflammatory cytokines such as INF-γand IL-17,which are produced by Th1 and Th17 cells,are elevated,while the levels of anti-inflammatory cytokines such as IL-4 and TGF-β,which are secreted by Th2 cells and regulatory T cells(Tregs),are diminished.Interventions using mesenchymal stem cells(MSCs)or their exosomes can alter the dynamics of helper T cell populations and their associated cytokine profiles,thereby mitigating the bone loss associated with periodontitis or even promoting bone regeneration.Mesenchymal stem cell-derived exosomes(MSC-exos)have been shown to directly modulate Th cell activity through the proteins and microRNAs they transport.Recent studies indicate that MSC-exos carry immune-suppressive protein molecules:PD-L1 and IDO contribute to regulating the balance between Th17 and Tregs;TGF-βinhibits the proliferation of T lymphocytes while facilitating differentiation into Tregs by sustaining forkhead box protein O3(FOXP3)and Smad expression;and CD73 catalyzes the conversion of monophosphate adenosine into adenosine,which interacts with A2A receptors on Th1 cells to induce apoptosis in Th1 cells.In addition,microRNAs exhibit immunoregulatory functions:periodontal ligament stem cell-derived exosomes contain miRNA-155-5p,which targets sirtuin-1 to suppress Th17 cell differentiation.Furthermore,evidence in rat models of periodonti-tis suggests that these exosomes may also carry miR-205-5p targeting XBP1 to restore the balance between Th17 and Tregs.Dental pulp stem cell-derived exosomes reestablish this balance via the miR-1246/Nfat5 axis.Bone marrow mesenchymal stem cell-derived exosomes harbor miR-1246,which targets ACE2 to promote differentiation towards Tregs.Moreover,MSC-exos can indirectly enhance the differentiation of Tregs through interactions with other immune entities,such as antigen-presenting cells or macrophages.This article reviews the changes and roles of helper T

关 键 词：牙周炎 辅助性T细胞 细胞因子 转录因子 间充质干细胞 外泌体 免疫调节 微小RNAS 

分 类 号：R78[医药卫生—口腔医学]