趋化因子受体CX3CR1促进单核来源朗格汉斯细胞亚群局部重建维持慢性皮肤炎症反应  

Chemokine receptor CX3CR1 promotes local remodeling of monocyte-derived Langerhans cell subsets to maintain chronic skin inflammation

作　　者：彭余 祝晓莉 张君 李传伟 宋文刚 唐华 徐英萍 Peng Yu;Zhu Xiaoli;Zhang Jun;Li Chuanwei;Song Wengang;Tang hua;Xu Yingping(Institute of Dermatology and Venereal Diseases,Dermatology Hospital of Southern Medical University,Guangzhou 510000,China;Institute of Immunology,Shandong First Medical University,Taian 271000,China)

机构地区：[1]南方医科大学皮肤病医院皮肤性病研究所,广州510000 [2]山东第一医科大学免疫学研究所,泰安271000

出　　处：《中华微生物学和免疫学杂志》2022年第4期302-309,共8页Chinese Journal of Microbiology and Immunology

基　　金：国家自然科学基金 (81471553,81872530)。

摘　　要：目的:探讨趋化因子受体CX3CR1在慢性皮肤炎症反应中的作用及调控机制。方法:通过二硝基氟苯诱导野生型(wild type,WT)和 Cx3 cr1 GFP/GFP基因缺陷小鼠制备急性和慢性变应性接触性皮炎(allergic contact dermatitis, ACD)模型,HE染色检测小鼠耳朵炎症变化及耳朵肿胀程度,流式细胞术(flow cytometry, FCM)分析小鼠表皮朗格汉斯细胞(Langerhans cell, LC)亚群包括经典LC和单核来源LC(monocyte-derived LC, Mo-LC)比例的变化,同时使用紫外线(ultraviolet, UV)照射诱导小鼠皮肤炎症反应模型进行相应细胞亚群的FCM分析;FCM分析Mo-LC表型及功能变化包括主要组织相容性复合体Ⅱ(major histocompatibility complex Ⅱ,MHCⅡ)、诱导型一氧化氮合酶(inducible nitric oxide synthase,iNOS)、TNF-α的表达水平。免疫组化法、定量RT-PCR和Western blot分析人慢性皮肤炎症组织中CX3CL1表达水平,免疫荧光染色检测CD1a、CD14及CD207表达。 结果:在慢性ACD模型中, Cx3 cr1 GFP/GFP小鼠耳朵炎性程度和肿胀程度比WT小鼠明显减轻,而在急性ACD模型中两组差异无统计学意义。Mo-LC细胞比例在慢性ACD模型及UV照射后期(3周)明显降低。此外,与经典LC比较,Mo-LC表达高水平MHCⅡ分子以及炎性因子TNF-α和iNOS。在人慢性皮肤炎症皮损组织中CX3CL1表达水平明显上调,CD14 +单核细胞、CD1a +Langerin -细胞明显增多。 结论:CX3CR1在慢性皮肤炎症中可能通过调控Mo-LC局部重建而维持炎症反应。Objective To investigate the role of chemokine receptor CX3CR1 in chronic skin inflammation and its regulatory mechanism.Methods Wild type(WT)C57BL/6 mice and Cx3cr1GFP/GFP mice were induced by DNFB to establish acute and chronic allergic contact dermatitis(ACD)model.Ear inflammation and swelling were observed with hematoxylin-eosin(HE)staining.Flow cytometry(FCM)was used to detect the changes in classical Langerhans cell(LC)and monocyte-derived LC(Mo-LC),as well as the expression of major histocompatibility complexⅡ(MHCⅡ),inducible nitric oxide synthase(iNOS)and TNF-α.Changes in epidermal LC in UV irradiation-induced dermatitis models were also analyzed.In human chronic skin inflammation,CX3CL1 expression was detected using immunohistochemistry,RT-PCR and Western blot and CD1a,CD14 and CD207 expression was observed with immunofluorescence staining.Results In the chronic ACD model,Cx3cr1GFP/GFP mice showed significantly alleviated ear inflammatory and swelling as compared with WT mice,but no significant difference was found in the acute ACD model.The percentages of Mo-LC were decreased in the chronic ACD model and after three weeks of UV irradiation.Moreover,MHCⅡ,TNF-αand iNOS expressed by Mo-LC were significantly upregulated as compared with those by classical LC.CX3CL1 expression was significantly upregulated and the numbers of CD14+monocytes and CD1a+langerin-Mo-LC were dramatically increased in human chronic skin inflammation.Conclusions CX3CR1 might maintain inflammatory response by regulating local remodeling of Mo-LC in chronic skin inflammation.

关 键 词：趋化因子受体CX3CR1 慢性皮肤炎症 单核来源朗格汉斯细胞亚群 炎症因子 免疫调控 

分 类 号：R392[医药卫生—免疫学]