摘要:树突状细胞 (dendritic cell,DC) 是已知能力最强的抗原提呈细胞 (antigen presenting cell,APC)。人 体中存在多种来源的 DC,髓系树突状细胞 (bone marrow-derived dendritic cells,BMDCs) 是免疫系统中重 要的细胞群之一,在肾脏急性肾损伤 (acute kidney injury,AKI) 发生时,BMDCs可以作为抗原提呈细胞激活 初始 T细胞,同时作为分泌肿瘤坏死因子 (tumor necrosis factor,TNF-α) 以及白细胞介素-10(interleukin- 10,IL-10) 等细胞因子影响炎性细胞浸润程度。BMDCs对炎性损伤以及肾脏组织修复具有促炎和抑炎的两重 作用。AKI是一种常见的临床综合征,后期易进展为慢性肾病 (chronic kidney disease,CKD),甚至终末期肾 病 (end stage renal disease,ESRD)。近年来 AKI 的发生率明显呈上升趋势,全球每年约有 1 300 余万例 AKI患者,其中约 170 万例患者死亡。缺血再灌注损伤 (ischemia reperfusion injury,IRI) 是 AKI的主要风险 因素之一。
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安哲昆,蔡明. 髓系树突状细胞参与肾缺血再灌注所致急性肾损伤的研究进展[J]. 泌尿外科杂志(电子版),2021,13(3):98-100,104. DOI:10.3969/j.issn.1674-7410.2021.03.024.
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急性肾损伤 (acute kidney injury,AKI) 作为 一种发病率及病死率较高的常见临床综合征,严重 影响病患预后。我国社区获得性 AKI (communityacquired acute kidney injury,CA-AKI) 和医院获 得 性 AKI (hospital- acquired acute kidney injury, HA-AKI) 的发生率分别为 2.5%和 9.1%[1] ,ICU 患 者中发生率甚至高达 31.7%[2] 。因此 IRI所致 AKI发 生后,树突状细胞 (dendritic cell,DC) 作为免疫 反应启动器之一,在免疫系统与肾小管上皮细胞等 肾脏细胞的相互作用中起着至关重要的作用,影响 着 AKI的结局[3-4] 。
髓系树突状细胞 (bone marrow- derived dendritic cells,BMDCs) 在 DC的多种亚型中,无论功 能和数量都是不可忽视的一个亚群[5] 。未成熟的树突 状细胞 (immature dendritic cells,imDCs) 具有迁 移及吞噬能力,但其表面缺乏 CD80、CD86、CD40 等共刺激因子,无法有效提呈抗原并完成对 T细胞的 激活[6] 。成熟的树突状细胞 (mature dendritic cells, mDCs) 表面组织相容性复合体Ⅱ (major histocompatibility complex-Ⅱ, MHC-Ⅱ)、CD83、CD11c、 CD80、CD86、CD40 等特异性抗原丰度较高[7] ,同 时还具备分泌肿瘤坏死因子-α(tumor necrosis factor-α,TNF-α) 及白细胞介素-10(interleukin-10, IL-10) 等细胞因子的能力,作为专职的抗原提呈细 胞 (antigen presenting cell,APC) 发挥免疫功能[8] 。
AKI发生后,BMDCs在肾脏炎性浸润、肾脏纤 维化以及肾功能恢复相关的固有免疫,以及适应性 免疫过程中发挥重要功能;BMDCs通过分泌多种细 胞因子与 T 细胞为主的淋巴细胞产生作用,激活或 抑制炎性浸润,并对 AKI发生后的肾功能恢复产生 影响[9] 。本文就 IRI 所致的 AKI 发生后,BMDCs 参 与免疫活动与肾损伤修复中的研究现状及研究前景 作一综述。
1 AKI 发生后 BMDCs 在炎性反应中的作用
1.1 BMDCs 的特异性抗原在 AKI 炎性反应中的作用
1.2 BMDCs与多种活性因子在 AKI相关炎性反应中的作用
2 IRI 所致 AKI 发生后,BMDCs 在肾功能恢复中 的作用
2.1 AKI 发生后 BMDCs 对肾功能恢复的抑制作用
2.2 BMDCs 促进 AKI 后肾功能恢复
3 展望
3 展望
目前对于 DC在肾脏 IRI所致的 AKI中效应呈现 出明显的两重效应。促进炎性反应进展主要体现在 促进炎性浸润以及增强肾小管上皮细胞 (tubular epithelial cells,TECs) 凋亡。通过分泌多种趋化因 子诱导免疫细胞,以及相关免疫活性物质向损伤部 位迁移、聚集,提高浸润程度,一方面加剧肾小管 上皮进一步损伤,另一方面降低损伤组织的修复能 力,但对于不同诱因导致的 AKI 其效应存在差异。 抗炎作用由 DC-10 实现,分别影响 T 细胞及 MAC 细胞向 Th1 型及 MI型 MAC 细胞极化,改变 IL-10 等细胞因子水平,但现有研究提示 DC的条件依赖的 抗炎作用。
综上所述,DC 在 IRI所致的 AKI中发挥重要的 免疫激活效应,主要表现为受 AKI损伤形式以及时 间进展影响的抗炎、抑炎两重效应。值得注意的 是,对于 DC 不同的免疫表型出现及出现的时间节 点,具有十分重要的现实意义。
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