Du Zhi-Hao, Chu Wei-Xia, Peng Xin, Wu Li-Ling, Liu Yan, Yu Guang-Yan, Ding Chong
Department of Oral and Maxillofacial Surgery, Peking University School and Hospital of Stomatology & National Center for Stomatology & National Clinical Research Center for Oral Diseases & National Engineering Research Center of Oral Biomaterials and Digital Medical Devices & Beijing Key Laboratory of Digital Stomatology & NHC Key Laboratory of Digital Stomatology & NMPA Key Laboratory for Dental Materials, No. 22, Zhongguancun South Avenue, Haidian District, Beijing 100081, P. R. China.
Center Laboratory, Peking University School and Hospital of Stomatology & National Center for Stomatology & National Clinical Research Center for Oral Diseases & National Engineering Research Center of Oral Biomaterials and Digital Medical Devices & Beijing Key Laboratory of Digital Stomatology & NHC Key Laboratory of Digital Stomatology & NMPA Key Laboratory for Dental Materials, No. 22, Zhongguancun South Avenue, Haidian District, Beijing 100081, P. R. China.
ACS Appl Mater Interfaces. 2025 Jan 29;17(4):5752-5761. doi: 10.1021/acsami.4c16595. Epub 2025 Jan 13.
: Sjögren's syndrome (SS), an autoimmune disease, was characterized by sicca syndrome and systemic manifestations, presenting significant treatment challenges. Exosomes, naturally derived nanoparticles containing bioactive molecules, have garnered interest in regenerative medicine. The present study aimed to elucidate the immunoregulatory properties and mechanism of exosomes obtained from the stem cells derived from human exfoliated deciduous teeth (SHED-exos) in SS-induced sialadenitis. : SHED-exo nanoparticles were injected into submandibular glands (SMGs) of 14-week-old nonobese diabetic (NOD) mice, a classic animal model of SS. At 21 weeks, the saliva flow rate (SFR) was measured. Lymphocyte proportions were examined via flow cytometry. Inflammatory cytokine levels were examined by the Quantibody mouse Th1/Th2/Th17 array and ELISA. miR-29a-3p expression and its regulatory effect on T-bet was detected using FISH and luciferase reporter gene assay, respectively. : SHED-exos injected into SMGs increased SFR, reduced lymphocytic infiltration, and decreased inflammatory cytokine levels in serum, SMG tissues, and saliva. Mechanistically, SHED-exos suppressed the Th1 proportion in spleen lymphocytes in NOD mice. Exosomal miR-29a-3p targeted and suppressed T-bet expression, which is a Th1-specific transcription factor. In vitro, SHED-exos (but not miR-29a-3p-inhibited exosomes) decreased the level of Th1 differentiation and IFN-γ and TNF-α production. Furthermore, SHED-exos (but not miR-29a-3p-inhibited exosomes) blocked the increase in IFN-γ and TNF-α production induced by T-bet overexpression. In vivo, miR-29a-3p-inhibited exosomes neither increase saliva secretion in NOD mice nor decrease lymphocytic infiltration, T-bet expression, and IFN-γ and TNF-α levels in SMGs. : SHED-exos suppress Th1 cell differentiation and response through the miR-29a-3p/T-bet axis, contributing to amelioration of SS-induced hyposalivation.
干燥综合征（SS）是一种自身免疫性疾病，其特征为口眼干燥综合征及全身表现，带来了重大的治疗挑战。外泌体是天然衍生的含有生物活性分子的纳米颗粒，已引起再生医学领域的关注。本研究旨在阐明从人脱落乳牙干细胞（SHED-exos）获得的外泌体在SS诱导的涎腺炎中的免疫调节特性及机制。：将SHED-exo纳米颗粒注射到14周龄非肥胖糖尿病（NOD）小鼠的下颌下腺（SMG）中，NOD小鼠是SS的经典动物模型。在21周时，测量唾液流速（SFR）。通过流式细胞术检测淋巴细胞比例。通过Quantibody小鼠Th1/Th2/Th17芯片和酶联免疫吸附测定（ELISA）检测炎性细胞因子水平。分别使用荧光原位杂交（FISH）和荧光素酶报告基因测定法检测miR-29a-3p的表达及其对T-bet的调节作用。：注射到SMG中的SHED-exos增加了SFR，减少了淋巴细胞浸润，并降低了血清、SMG组织和唾液中的炎性细胞因子水平。机制上，SHED-exos抑制了NOD小鼠脾脏淋巴细胞中Th1的比例。外泌体miR-29a-3p靶向并抑制T-bet的表达，T-bet是一种Th1特异性转录因子。在体外，SHED-exos（但不是miR-29a-3p抑制的外泌体）降低了Th1分化水平以及IFN-γ和TNF-α的产生。此外，SHED-exos（但不是miR-29a-3p抑制的外泌体）阻断了由T-bet过表达诱导的IFN-γ和TNF-α产生的增加。在体内，miR-29a-3p抑制的外泌体既未增加NOD小鼠的唾液分泌，也未降低SMG中的淋巴细胞浸润、T-bet表达以及IFN-γ和TNF-α水平。：SHED-exos通过miR-29a-3p/T-bet轴抑制Th1细胞分化和反应，有助于改善SS诱导的唾液分泌减少。
