Yang Ning, Liu Xuemei, Chen Xu, Yu Si, Yang Wenxiao, Liu Yao
Department of Pediatric Dentistry, School and Hospital of Stomatology, China Medical University, Shenyang, China.
Liaoning Provincial Key Laboratory of Oral Diseases, Shenyang, China.
J Leukoc Biol. 2022 May;111(5):1043-1055. doi: 10.1002/JLB.6MA0921-752RR. Epub 2021 Oct 8.
Mesenchymal stem cell transplantation (MSCT) regulates immune cells, and is a promising therapeutic approach for treating autoimmune diseases. Stem cells from human exfoliated deciduous teeth (SHED) are a unique postnatal stem cell population from the cranial neural crest with high self-renewal, multipotent differentiation, and superior immunomodulatory properties. However, the mechanisms by which SHED can treat autoimmune diseases remain unclear. Sjögren's syndrome (SS) is an autoimmune disease histologically characterized by high lymphocytic infiltration in the salivary and lacrimal glands that results in dryness symptoms. This study explores the potential of systemic transplantation of SHED to ameliorate SS-induced dryness symptoms in mice. Overall, SHED could rescue the balance of regulatory T cell (Treg)/T helper cell 17 (Th17) in the recipient SS mice. Mechanistically, SHED promoted Treg conversion and inhibited Th17 function via paracrine effects, which were related to the secretion of soluble programmed cell death ligand 1 (sPD-L1). Moreover, it directly induced Th17 apoptosis via cell-cell contact, leading to the up-regulation of Treg and down-regulation of Th17 cells. In summary, SHED-mediated rescue of Treg/Th17 balance via the sPD-L1/PD-1 pathway ameliorates the gland inflammation and dryness symptoms in SS mice. These findings suggest that SHED are a promising stem cell source for the treatment of autoimmune diseases in the clinical setting.
间充质干细胞移植（MSCT）可调节免疫细胞，是治疗自身免疫性疾病的一种有前景的治疗方法。人脱落乳牙干细胞（SHED）是一种独特的出生后干细胞群体，来源于颅神经嵴，具有高度自我更新、多能分化和卓越的免疫调节特性。然而，SHED治疗自身免疫性疾病的机制仍不清楚。干燥综合征（SS）是一种自身免疫性疾病，组织学特征为唾液腺和泪腺中淋巴细胞高度浸润，导致干燥症状。本研究探讨了全身移植SHED改善小鼠SS诱导的干燥症状的潜力。总体而言，SHED可恢复受体SS小鼠中调节性T细胞（Treg）/辅助性T细胞17（Th17）的平衡。机制上，SHED通过旁分泌作用促进Treg转化并抑制Th17功能，这与可溶性程序性细胞死亡配体1（sPD-L1）的分泌有关。此外，它通过细胞间接触直接诱导Th17凋亡，导致Treg上调和Th17细胞下调。总之，SHED通过sPD-L1/PD-1途径介导的Treg/Th17平衡的恢复改善了SS小鼠的腺体炎症和干燥症状。这些发现表明，SHED是临床环境中治疗自身免疫性疾病的一种有前景的干细胞来源。
