外泌体是由细胞分泌的一种膜性囊泡,可广泛参与细胞间通讯、抗炎、免疫调节等。眼表相关的外泌体来源细胞有间充质干细胞(MSC)、调节性T细胞(Treg)、未成熟树突状细胞(imDC)和髓源性抑制细胞(MDSC)。不同细胞来源的外泌体通过递送不同的生物分子给受体细胞而发挥作用。MSC来源的外泌体通过抑制T细胞增生、转换巨噬细胞表型、调控辅助性T(Th)细胞分化、上调Treg表达等机制对眼表炎症与免疫相关疾病有积极作用,同时可减少新生血管和炎症反应,培育了一个可促进角膜损伤修复的微环境。Treg来源外泌体内含微小RNA(miRNA)(miR-503、miR-330和miR-9)和诱导型NO合成酶,可通过干扰细胞周期进程,诱导凋亡和其他T细胞分化为Treg表型,抑制T细胞的同种异体排斥反应从而诱导免疫耐受。imDC来源外泌体通过递送miR-682抑制角膜植片免疫排斥。MDSC来源外泌体在体内外促进Treg扩增,抑制活化T细胞的增生和细胞毒性反应,还表达miR-29a-3p和miR-93-5p,可抑制Th1和Th17细胞分化。鉴于上述外泌体的抗炎及免疫抑制作用,本文就其对眼表炎症与免疫相关疾病如角膜损伤、黏多糖贮积症、干眼、干燥综合征和眼部移植物抗宿主病等的研究进行综述。
Exosomes are membranous vesicles secreted by cells and can be widely involved in intercellular communication, anti-inflammation, immunoregulation, etc.Mesenchymal stem cell (MSC), regulatory T cell (Treg), immature dendritic cell (imDC) and myeloid-derived suppressor cell (MDSC) are the main ocular surface-related exosomes origins.Exosomes derived from different cells play their roles by delivering different biological molecules to recipient cells.Exosomes derived from MSC play a positive role in ocular surface inflammation and immune-related diseases by inhibiting T cell proliferation, transforming macrophage phenotype, regulating T helper (Th) cell differentiation and up-regulating Treg expression, reduce neovascularization and inflammation, and foster a microenvironment to promote corneal wound healing at the same time.Exosomes derived from Treg contain inducible NO synthase and microRNA (miRNA) including miR-503, miR-330 and miR-9, which can interfere with cell cycle progression, induce apoptosis, induce the differentiation of other T cells into Treg phenotype, inhibit T cell allograft rejection to induce immune tolerance.Exosomes derived from imDC inhibit corneal allograft rejection by delivering miR-682.MDSC-derived exosomes promote Treg expansion in vivo and in vitro, inhibit the proliferation and cytotoxicity of activated T cells, and express miR-29a-3p and miR-93-5p, which can inhibit the differentiation of Th1 and Th17 cells.Given the anti-inflammatory and immunosuppressive effects of exosomes, this paper reviewed the studies on ocular surface inflammation and immune-related diseases such as corneal injury, mucopolysaccharide storage disease, dry eye, Sjögren syndrome and ocular graft-versus-host disease.
康艺龄,赵少贞. 不同细胞来源外泌体对眼表的作用研究进展[J]. 中华实验眼科杂志,2022,40(08):766-770.
DOI:10.3760/cma.j.cn115989-20200419-00271版权归中华医学会所有。
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