皮肤<b>γδ</b>T细胞各亚群在创面再上皮化过程中的调控作用及其相关机制

贺伟峰

doi:10.3760/cma.j.cn501120-20211210-00411

皮肤γδT细胞各亚群在创面再上皮化过程中的调控作用及其相关机制

doi: 10.3760/cma.j.cn501120-20211210-00411

贺伟峰^,

陆军军医大学（第三军医大学）第一附属医院全军烧伤研究所，创伤、烧伤与复合伤国家重点实验室，重庆市创面修复与组织再生重点实验室,重庆　　400038

基金项目:

国家自然科学基金面上项目 31872742, 82172232

军队医学科技青年培育计划 20QNPY024

陆军军医大学科技创新能力提升专项 2019XQY12

详细信息

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Email：whe761211@hotmail.com

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出版历程
- 收稿日期: 2021-12-10

Regulatory role and related mechanism of skin gamma-delta T cell subsets in wound re-epithelialization

He Weifeng^,

State Key Laboratory of Trauma, Burns and Combined Injury, Institute of Burn Research, the First Affiliated Hospital of Army Medical University (the Third Military Medical University), Chongqing Key Laboratory for Wound Repair and Regeneration, Chongqing 400038, China

Funds:

General Program of National Natural Science Foundation of China 31872742, 82172232

Military Medical Science and Technology Youth Training Program 20QNPY024

Science and Technology Innovation Capability Improvement Project of Army Military Medical University 2019XQY12

More Information

Corresponding author: Email: whe761211@hotmail.com

摘要

摘要:
再上皮化过程是决定皮肤创面愈合进程的核心环节之一。表皮干细胞增殖分化形成新生表皮组织是再上皮化的组织学基础，而表皮干细胞—前体细胞—终末细胞这一细胞分化过程顺利进行是新生表皮组织不断形成的细胞学基础。表皮干细胞增殖及分化为前体细胞是新生表皮组织增殖潜力的决定因素，而前体细胞扩增及分化为终末细胞是决定新生表皮组织形成速度的关键因素。组织微环境在创面再上皮化过程中发挥关键的调控作用，而细胞生长因子和炎症介质是构成创面组织微环境的2个重要组成成分，分别在表皮干细胞增殖分化的不同环节发挥调节作用，协同促进创面再上皮化顺利进行。γδT细胞是皮肤免疫系统中的重要组成部分，其不同亚群分别通过分泌生长因子和炎症因子在动态塑造早期创面微环境中起关键作用。本文从创面免疫微环境的角度出发，简要论述皮肤γδT细胞在维持表皮干细胞增殖分化平衡以及调控创面再上皮化中的作用，为难愈性创面的预防及治疗提供新方向。
- 皮肤 /
- 伤口愈合 /
- 再上皮化 /
- 表皮干细胞 /
- 免疫微环境 /
- γδT细胞
Abstract:
Re-epithelialization is one of the core links that determines the healing process of skin wounds. The proliferation and differentiation of epidermal stem cells to form new epidermal tissue is the histological basis of re-epithelialization, and the smooth progress of the cell differentiation process of epidermal stem cells-precursor cells-terminal cells is the cytological basis for the continuous formation of new epidermal tissue. The proliferation of stem cells and their differentiation into precursor cells are the determinants of the proliferative potential of newly formed epidermal tissue, while the expansion and differentiation of precursor cells into terminal cells are key factors determining the rate of new epidermal tissue formation. The tissue microenvironment plays a key regulatory role in the process of wound re-epithelialization, and cell growth factor and inflammatory mediators are the two main components of tissue microenvironment, which play regulatory role in different aspects of proliferation and differentiation of epidermal stem cells, jointly promoting the smooth progress of wound re-epithelialization As an important part of skin immune system, the subsets of gamma-delta (γδ) T cells play crucial role in dynamically shaping early wound microenvironment via secreting different cell growth factors and inflammatory factors. From the prospective of immune microenvironment of wound, this paper discusses the role of skin γδ T cells in maintaining the balance of stem cell proliferation and differentiation and regulating wound re-epithelialization, providing a new direction for the prevention and treatment of refractory wound.
- Skin /
- Wound healing /
- Re-epitheliali- zation /
- Epidermal stem cells /
- Immune microenvironment /
- Gamma-delta T cells
作者声明不存在利益冲突

烧伤最普遍的并发症之一就是创面恶化，其特征是未经治疗的创面组织持续被破坏，导致创面感染、炎症、氧化应激和瘢痕过度形成。美国得克萨斯州州立大学David N. Herndon教授联合医学部外科系、生物化学与分子生物系和麻醉系科研人员近期在《Burns & Trauma》发文《Metal chelation reduces skin epithelial inflammation and rescues epithelial cells from toxicity due to thermal injury in a rat model》，该文选用SD大鼠建立2%TBSA烧伤模型进行创面研究，造模后每8小时局部涂抹Livionex配方（LF）洗剂（含乙二胺四乙酸和甲基磺酰甲烷），持续3 d，观察假手术对照组（单纯备皮，既未烧伤也未使用LF洗剂）、单纯烧伤组和烧伤后LF洗剂处理组大鼠炎症细胞因子水平、细胞凋亡和创面愈合情况。3 d后并未在单纯烧伤组大鼠和烧伤后LF洗剂处理组大鼠血清中检测到炎症因子产生，表明小面积烧伤创面仅诱发了一过性的、局部的炎症反应。显微镜下观察显示，与单纯烧伤组相比，烧伤后LF洗剂处理组大鼠烧伤部位的病理状况明显改善。原位末端转移酶标记染色实验结果显示，与单纯烧伤组相比，烧伤后LF洗剂处理组大鼠创面组织中细胞凋亡减少，邻近表皮和毛囊中Ki-67阳性核的数量增加，表明LF洗剂防止了组织损伤的扩散。在烧伤后LF洗剂处理组大鼠皮肤切片中，TNF-α、IL-6和诱生型NOS的水平与假手术对照组大鼠相当，证明LF洗剂可减少烧伤部位及其周围的炎症。此项研究结果表明，烧伤后立即使用LF洗剂可减轻炎症应激、细胞凋亡和组织破坏。LF洗剂是否能作为一种改善预后和瘢痕产生的治疗方法，还需进一步在大面积烧伤模型中进行研究。

杨云稀，编译自《Burns & Trauma》，2020，8: tkaa024；孙炳伟，审校

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参考文献(37)

[1]	MacLeodAS,HemmersS,GarijoO,et al.Dendritic epidermal T cells regulate skin antimicrobial barrier function[J].J Clin Invest,2013,123(10):4364-4374.DOI: 10.1172/JCI70064.
[2]	MunozLD,SweeneyMJ,JamesonJM.Skin resident γδ T Cell function and regulation in wound repair[J].Int J Mol Sci,2020, 21(23):9286 DOI: 10.3390/ijms21239286.
[3]	ReinkeJM, SorgH. Wound repair and regeneration[J]. Eur Surg Res,2012,49(1):35-43. DOI: 10.1159/000339613.
[4]	KucharzewskiM,RojczykE,Wilemska-KucharzewskaK,et al.Novel trends in application of stem cells in skin wound healing[J].Eur J Pharmacol,2019,843:307-315.DOI: 10.1016/j.ejphar.2018.12.012.
[5]	YangR,LiuF,WangJ,et al.Epidermal stem cells in wound healing and their clinical applications[J].Stem Cell Res Ther,2019,10(1):229.DOI: 10.1186/s13287-019-1312-z.
[6]	DekoninckS,BlanpainC.Stem cell dynamics, migration and plasticity during wound healing[J].Nat Cell Biol,2019,21(1):18-24.DOI: 10.1038/s41556-018-0237-6.
[7]	KanjiS,DasH.Advances of stem cell therapeutics in cutaneous wound healing and regeneration[J].Mediators Inflamm,2017,2017:5217967.DOI: 10.1155/2017/5217967.
[8]	YangR,WangJ,ChenX,et al.Epidermal stem cells in wound healing and regeneration[J].Stem Cells Int,2020,2020:9148310.DOI: 10.1155/2020/9148310.
[9]	XiaoT,YanZ,XiaoS,et al.Proinflammatory cytokines regulate epidermal stem cells in wound epithelialization[J].Stem Cell Res Ther,2020,11(1):232.DOI: 10.1186/s13287-020-01755-y.
[10]	LiY,WuJ,LuoG,et al.Functions of Vγ4 T cells and dendritic epidermal T cells on skin wound healing[J].Front Immunol,2018,9:1099.DOI: 10.3389/fimmu.2018.01099.
[11]	SharpLL,JamesonJM,CauviG,et al.Dendritic epidermal T cells regulate skin homeostasis through local production of insulin-like growth factor 1[J].Nat Immunol,2005,6(1):73-79.DOI: 10.1038/ni1152.
[12]	ChenWY,RogersAA.Recent insights into the causes of chronic leg ulceration in venous diseases and implications on other types of chronic wounds[J].Wound Repair Regen,2007,15(4):434-449.DOI: 10.1111/j.1524-475X.2007.00250.x.
[13]	FrykbergRG,BanksJ.Challenges in the treatment of chronic wounds[J].Adv Wound Care (New Rochelle),2015,4(9):560-582.DOI: 10.1089/wound.2015.0635.
[14]	KhannaS,BiswasS,ShangY,et al.Macrophage dysfunction impairs resolution of inflammation in the wounds of diabetic mice[J].PLoS One,2010,5(3):e9539.DOI: 10.1371/journal.pone.0009539.
[15]	JanuszykM,SorkinM,GlotzbachJP,et al.Diabetes irreversibly depletes bone marrow-derived mesenchymal progenitor cell subpopulations[J].Diabetes,2014,63(9):3047-3056.DOI: 10.2337/db13-1366.
[16]	LermanOZ,GalianoRD,ArmourM,et al.Cellular dysfunction in the diabetic fibroblast: impairment in migration, vascular endothelial growth factor production, and response to hypoxia[J].Am J Pathol,2003,162(1):303-312.DOI: 10.1016/S0002-9440(10)63821-7.
[17]	RodriguesM,KosaricN,BonhamCA,et al.Wound healing: a cellular perspective[J].Physiol Rev,2019,99(1):665-706.DOI: 10.1152/physrev.00067.2017.
[18]	XiangJ,QiuM,ZhangH.Role of dendritic epidermal T cells in cutaneous carcinoma[J].Front Immunol,2020,11:1266.DOI: 10.3389/fimmu.2020.01266.
[19]	谈思怡,向征,徐艳,等.人γδ T细胞的抗肿瘤临床免疫治疗新进展[J].生命科学,2017,29(9):855-863.DOI: 10.13376/j.cbls/2017115.
[20]	ChodaczekG,PapannaV,ZalMA,et al.Body-barrier surveillance by epidermal γδ TCRs[J].Nat Immunol,2012,13(3):272-282.DOI: 10.1038/ni.2240.
[21]	EdelbaumD,MohamadzadehM,BergstresserPR,et al.Interleukin (IL)-15 promotes the growth of murine epidermal gamma delta T cells by a mechanism involving the beta- and gamma c-chains of the IL-2 receptor[J].J Invest Dermatol,1995,105(6):837-843.DOI: 10.1111/1523-1747.ep12326630.
[22]	XuY,DimitrionP,CvetkovskiS,et al.Epidermal resident γδ T cell development and function in skin[J].Cell Mol Life Sci,2021,78(2):573-580.DOI: 10.1007/s00018-020-03613-9.
[23]	陈成,胡晓红,梁光萍,等.DETC在创面愈合过程中对炎症反应的调控作用及机制研究进展[J/CD].中华细胞与干细胞杂志:电子版,2020,10(6):378-382.DOI: 10.3877/cma.j.issn.2095-1221.2020.06.011.
[24]	LiY,WangY,ZhouL,et al.Vγ4 T cells inhibit the pro-healing functions of dendritic epidermal T cells to delay skin wound closure through IL-17A[J].Front Immunol,2018,9:240.DOI: 10.3389/fimmu.2018.00240.
[25]	LiuZ,LiangG,GuiL,et al.Weakened IL-15 production and impaired mTOR activation alter dendritic epidermal T cell homeostasis in diabetic mice[J].Sci Rep,2017,7(1):6028.DOI: 10.1038/s41598-017-05950-5.
[26]	BodurC,KazykenD,HuangK,et al.The IKK-related kinase TBK1 activates mTORC1 directly in response to growth factors and innate immune agonists[J].EMBO J,2018,37(1):19-38.DOI: 10.15252/embj.201696164.
[27]	ChoML,KangJW,MoonYM,et al.STAT3 and NF-kappaB signal pathway is required for IL-23-mediated IL-17 production in spontaneous arthritis animal model IL-1 receptor antagonist- deficient mice[J].J Immunol,2006,176(9):5652-5661.DOI: 10.4049/jimmunol.176.9.5652.
[28]	ChenY,ZhangX,LiuZ,et al.Obstruction of the formation of granulation tissue leads to delayed wound healing after scald burn injury in mice[J/OL].Burns Trauma,2021,9:tkab004 [2022-01-21]. https://pubmed.ncbi.nlm.nih.gov/34212057.DOI: 10.1093/burnst/tkab004.
[29]	Muñoz-RuizM,SumariaN,PenningtonDJ,et al.Thymic determinants of γδ T cell differentiation[J].Trends Immunol,2017,38(5):336-344.DOI: 10.1016/j.it.2017.01.007.
[30]	GiriS,LalG.Differentiation and functional plasticity of gamma-delta (γδ) T cells under homeostatic and disease conditions[J].Mol Immunol,2021,136:138-149.DOI: 10.1016/j.molimm.2021.06.006.
[31]	RoderoMP,HodgsonSS,HollierB,et al.Reduced Il17a expression distinguishes a Ly6cloMHCIIhi macrophage population promoting wound healing[J].J Invest Dermatol,2013,133(3):783-792.DOI: 10.1038/jid.2012.368.
[32]	MillsRE,TaylorKR,PodshivalovaK,et al.Defects in skin gamma delta T cell function contribute to delayed wound repair in rapamycin-treated mice[J].J Immunol,2008,181(6):3974-3983.DOI: 10.4049/jimmunol.181.6.3974.
[33]	MartinP,NunanR.Cellular and molecular mechanisms of repair in acute and chronic wound healing[J].Br J Dermatol,2015,173(2):370-378.DOI: 10.1111/bjd.13954.
[34]	Ramírez-ValleF,GrayEE,CysterJG.Inflammation induces dermal Vγ4+ γδT17 memory-like cells that travel to distant skin and accelerate secondary IL-17-driven responses[J].Proc Natl Acad Sci U S A,2015,112(26):8046-8051.DOI: 10.1073/pnas.1508990112.
[35]	MaedaY,SekiN,KataokaH,et al.IL-17-producing Vγ4+ γδ T cells require sphingosine 1-phosphate receptor 1 for their egress from the lymph nodes under homeostatic and inflammatory conditions[J].J Immunol,2015,195(4):1408-1416.DOI: 10.4049/jimmunol.1500599.
[36]	RaverdeauM,CunninghamSP,HarmonC,et al.γδ T cells in cancer: a small population of lymphocytes with big implications[J].Clin Transl Immunology,2019,8(10):e01080.DOI: 10.1002/cti2.1080.
[37]	TengM,HuangY,ZhangH.Application of stems cells in wound healing--an update[J].Wound Repair Regen,2014,22(2):151-160.DOI: 10.1111/wrr.12152.