Email Alerts
RSS
Volume 40 Issue 5
May  2024
Turn off MathJax
Article Contents
Article Navigation >  CHINESE JOURNAL OF BURNS AND WOUNDS  > 2024  >  40(5): 415-424
Li YS,He WF,Lyu KY.Role and mechanism of Vγ4 T cell depletion in epidermal tissue repair after ultraviolet damage to mouse skin[J].Chin J Burns Wounds,2024,40(5):415-424.DOI: 10.3760/cma.j.cn501225-20240121-00026.
Citation: Li YS,He WF,Lyu KY.Role and mechanism of Vγ4 T cell depletion in epidermal tissue repair after ultraviolet damage to mouse skin[J].Chin J Burns Wounds,2024,40(5):415-424.DOI: 10.3760/cma.j.cn501225-20240121-00026.
shu

Role and mechanism of Vγ4 T cell depletion in epidermal tissue repair after ultraviolet damage to mouse skin

doi: 10.3760/cma.j.cn501225-20240121-00026
  • 1.

    Department of Plastic Surgery, Xinhua Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200092, China

  • 2.

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

Funds:

Youth Science Fund Program of National Natural Science Foundation of China 32000645

More Information
    Abstract
  •   Objective  To explore the role and mechanism of Vγ4 T cell depletion in epidermal tissue repair after ultraviolet damage to mouse skin.  Methods  The study was an experimental study. Fifty-four female C57BL/6J wild-type mice aged 6 to 8 weeks were divided into Vγ4 T cell depletion group and control group (27 mice in each group) according to the random number table, and the Armenian hamster anti-mouse Vγ4 T cell receptor (TCR) monoclonal antibody of 200 µg and an equal amount of homologous control IgG antibody were intraperitoneally injected, respectively. At one week after injection (the same time point to harvest mice below), dermal cells and lymph node cells were respectively extracted from the back skin tissue, armpit and inguinal lymph nodes of 3 mice in each group (mice in following study were all taken from these 2 groups), and the proportions of Vγ4 T cells in dermal cells and lymph node cells were detected by flow cytometry. Five mice from each group were harvested for observation of skin on the back and skin tissue structure was observed and the epidermal tissue thickness was measured after hematoxylin-eosin (HE) staining. Five mice from each group were harvested for detection of proportion of dendritic epidermal T cells (DETCs) in epidermal cells by flow cytometry after extracted. Three mice were taken from each group and recruited in Vγ4 T cell depletion+5 times ultraviolet irradiation (UVR) group and control+5 times UVR group, respectively, then UVR was administered once per day for 5 times, and the condition of skin on the back was observed immediately after daily irradiation. Five mice were taken from each group and divided into Vγ4 T cell depletion+1 UVR group and control+1 UVR group, respectively. Immediately after one UVR treatment, the epidermal tissue thickness was measured after HE staining. Three mice from each group were selected and recruited in Vγ4 T cell depletion alone group and control alone group, then 3 mice from each group rwere recruited in Vγ4 T cell depletion+1 time UVR group and control+1 time UVR group, respectively, and were treated as before. The mRNA expressions of insulin-like growth factor-Ⅰ (IGF-Ⅰ), keratinocyte growth factor (KGF), Vγ5 TCR, interleukin-15 (IL-15), IL-1β, IL-23, natural killer group 2 member D (NKG2D), histocompatibility antigen 60 (H60), mouse UL16-binding protein-like transcript 1 (Mult1), and retinoic acid early inducible protein 1 (Rae1) in the epidermal tissue were detected by real-time fluorescent quantitative reverse transcription polymerase chain reaction.  Results  At one week after injection, the proportions of Vγ4 T cells in dermal cells and lymph node cells of mice in Vγ4 T cell depletion group were significantly lower than those in control group (with t values of 27.99 and 13.12, respectively, P<0.05); there were no statistically significant differences in the skin general condition and tissue structure of mice between Vγ4 T cell depletion group and control group; the epidermal tissue thickness of mice between Vγ4 T cell depletion group and control group was similar (P>0.05); the proportion of DETCs in epidermal cells of mice in Vγ4 T cell depletion group was (3.9±0.8)%, which was significantly higher than (1.6±0.5)% in control group (t=4.84, P<0.05). Compared with that in control+5 times UVR group, the skin scale increased after one UVR treatment, scaly scab appeared after 2 times of irradiation, and scaly scab increased significantly after 3 to 5 times of irradiation in Vγ4 T cell depletion+5 times UVR group. Immediately after UVR treatment, the epidermal tissue thickness of mice in Vγ4 T cell depletion+1 time UVR group was significantly increased compared with that in control+1 time UVR group (t=11.50, P<0.05). Compared with those in control alone group, the mRNA expression of Vγ5 TCR in the epidermal tissue of mice in Vγ4 T cell depletion alone group was up-regulated (t=41.16, P<0.05), while the mRNA expression of IL-23 was down-regulated (t=6.52, P<0.05); compared with those in control alone group, the mRNA expressions of Vγ5 TCR and KGF in the epidermal tissue of mice in control+1 time UVR group were significantly up-regulated (with t values of 15.22 and 13.22, respectively, P<0.05), while the mRNA expressions of IGF-Ⅰ and IL-23 were significantly down-regulated (with t values of 3.71 and 4.95, respectively, P<0.05); compared with those in Vγ4 T cell depletion alone group, the mRNA expressions of IGF-Ⅰ and KGF in the epidermal tissue of mice in Vγ4 T cell depletion+1 time UVR group were significantly up-regulated (with t values of 11.40 and 18.88, respectively, P<0.05), while the mRNA expression of IL-1β was significantly down-regulated (t=4.42, P<0.05); compared with those in control+1 time UVR group, the mRNA expressions of Vγ5 TCR, IGF-Ⅰ, and KGF in the epidermal tissue of mice in Vγ4 T cell depletion+1 time UVR group were significantly up-regulated (with t values of 4.52, 15.24, and 9.43, respectively, P<0.05); the mRNA expression of IL-15 in the epidermal tissue of mice in these 4 groups was generally similar (P>0.05). Compared with those in control alone group, the mRNA expressions of NKG2D and Rae1 in the epidermal tissue of mice in Vγ4 T cell depletion alone group were significantly up-regulated (with t values of 3.67 and 47.40, respectively, P<0.05), the mRNA expressions of NKG2D, Mult1, and Rae1 in the epidermal tissue of mice in control+1 time UVR group were significantly up-regulated (with t values of 5.30, 6.50, and 9.16, respectively, P<0.05); compared with those in Vγ4 T cell depletion alone group, the mRNA expressions of NKG2D, H60, Mult1, and Rae1 in the epidermal tissue of mice in Vγ4 T cell depletion+1 time UVR group were significantly down-regulated (with t values of 4.57, 4.13, 4.67, and 27.36, respectively, P<0.05); compared with those in control group+1 time UVR group, the mRNA expressions of NKG2D, H60, Mult1, and Rae1 in the epidermal tissue of mice in Vγ4 T cell depletion+1 time UVR group were significantly down-regulated (with t values of 5.77, 8.18, 12.90, and 8.08, respectively, P<0.05).  Conclusions  The clearance of Vγ4 T cells is conducive to the proliferation and down-regulation of cytotoxicity of DETCs, and may promote the repair of mouse epidermal damage after UVR.

     

    • FullText(HTML)
  • loading
    • References(31)
  • [1]
    WittlichM, WesterhausenS, StrehlB, et al. The GENESIS-UV study on ultraviolet radiation exposure levels in 250 occupations to foster epidemiological and legislative efforts to combat nonmelanoma skin cancer[J]. Br J Dermatol, 2023,188(3):350-360. DOI: 10.1093/bjd/ljac093.
    [2]
    Castejón-GriñánM, CerdidoS, Sánchez-BeltránJ, et al. Melanoma-associated melanocortin 1 receptor variants confer redox signaling-dependent protection against oxidative DNA damage[J]. Redox Biol, 2024,72: 103135. DOI: 10.1016/j.redox.2024.103135.
    [3]
    SlominskiRM,ChenJY,RamanC,et al.Photo-neuro-immuno-endocrinology: how the ultraviolet radiation regulates the body, brain, and immune system[J].Proc Natl Acad Sci U S A,2024,121(14):e2308374121.DOI: 10.1073/pnas.2308374121.
    [4]
    FrascoliM, FerrajE, MiuB, et al. Skin γδ T cell inflammatory responses are hardwired in the thymus by oxysterol sensing via GPR183 and calibrated by dietary cholesterol[J]. Immunity, 2023,56(3):562-575.e6. DOI: 10.1016/j.immuni.2023.01.025.
    [5]
    WeiYX,SunGY,YangY,et al.Double-negative T cells ameliorate psoriasis by selectively inhibiting IL-17A-producing γδlow T cells[J].J Transl Med,2024,22(1):328.DOI: 10.1186/s12967-024-05132-8.
    [6]
    PeslierH,ReichartJ,BoursotC,et al.Extensive cutaneous-mucosal and muscular involvement of gamma/delta cutaneous T-cell lymphoma on 18F-FDG PET/CT[J].Clin Nucl Med,2024,49(5):e206-e207.DOI: 10.1097/RLU.0000000000005135.
    [7]
    YangYL, ZhouC, ChenQ, et al. YAP1/Piezo1 involve in the dynamic changes of lymphatic vessels in UVR-induced photoaging progress to squamous cell carcinoma[J]. J Transl Med, 2023,21(1):820. DOI: 10.1186/s12967-023-04458-z.
    [8]
    HarmonC, ZaborowskiA, MooreH, et al. γδ T cell dichotomy with opposing cytotoxic and wound healing functions in human solid tumors[J]. Nat Cancer, 2023,4(8):1122-1137. DOI: 10.1038/s43018-023-00589-w.
    [9]
    PetrovićJ,SilvaJR,BannermanCA,et al.γδ T cells modulate myeloid cell recruitment but not pain during peripheral inflammation[J].Front Immunol,2019,10:473.DOI: 10.3389/fimmu.2019.00473.
    [10]
    SonomotoK,SongR,ErikssonD,et al.High-fat-diet‐associated intestinal microbiota exacerbates psoriasis-like inflammation by enhancing systemic γδ T cell IL-17 production[J].Cell Rep,2023,42(7):112713.DOI: 10.1016/j.celrep.2023.112713.
    [11]
    LiuM, LiuZH, ChenYX, et al. Dendritic epidermal T cells secreting exosomes promote the proliferation of epidermal stem cells to enhance wound re-epithelialization[J]. Stem Cell Res Ther, 2022,13(1):121. DOI: 10.1186/s13287-022-02783-6.
    [12]
    ChenC, MengZY, RenH, et al. The molecular mechanisms supporting the homeostasis and activation of dendritic epidermal T cell and its role in promoting wound healing[J/OL]. Burns Trauma, 2021,9:tkab009[2024-01-21]. https://pubmed.ncbi.nlm.nih.gov/34212060/.DOI: 10.1093/burnst/tkab009.
    [13]
    ThelenF, WitherdenDA. Get in touch with dendritic epithelial T cells![J]. Front Immunol, 2020,11:1656. DOI: 10.3389/fimmu.2020.01656.
    [14]
    HeiligJS, TonegawaS. Diversity of murine gamma genes and expression in fetal and adult T lymphocytes[J]. Nature, 1986,322(6082):836-840. DOI: 10.1038/322836a0.
    [15]
    LiYS, WuJ, LuoGX, 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.
    [16]
    王珏, 张小容, 贺伟峰, 等. 树突状表皮T细胞在创面愈合中作用机制的研究进展[J].中华烧伤杂志,2021,37(3):296-300. DOI: 10.3760/cma.j.cn501120-20200226-00092.
    [17]
    LiYS, WangYP, ZhouLN, 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.
    [18]
    YangBW, LinYM, HuangYB, et al. Extracellular vesicles modulate key signalling pathways in refractory wound healing[J/OL]. Burns Trauma, 2023,11:tkad039[2024-01-21].https://pubmed.ncbi.nlm.nih.gov/38026441/.DOI: 10.1093/burnst/tkad039.
    [19]
    LiuZY,LiangGP,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.
    [20]
    Dhillon-LaBrooyA, BrabandKL, TantawyE, et al. Inhibition of mitochondrial translation ameliorates imiquimod-induced psoriasis-like skin inflammation by targeting Vγ4+ γδ T cells[J]. J Invest Dermatol, 2024,144(4):844-854.e2. DOI: 10.1016/j.jid.2023.09.275.
    [21]
    LiYS, WangJ, WangYP, et al. IL-1β/NF-κB signaling inhibits IGF-1 production via let-7f-5p in dendritic epidermal T cells[J]. J Leukoc Biol, 2022,112(6):1677-1690. DOI: 10.1002/JLB.3MA0322-171R.
    [22]
    LiYS, HuangZG, YanRS, et al. Vγ4 γδ T cells provide an early source of IL-17A and accelerate skin graft rejection[J]. J Invest Dermatol, 2017,137(12):2513-2522. DOI: 10.1016/j.jid.2017.03.043.
    [23]
    WeiXR, LiMX, ZhengZJ, et al. Senescence in chronic wounds and potential targeted therapies[J/OL]. Burns Trauma, 2022,10:tkab045[2024-01-21]. https://pubmed.ncbi.nlm.nih.gov/35187179/.DOI: 10.1093/burnst/tkab045.
    [24]
    NitaharaA, ShimuraH, ItoA, et al. NKG2D ligation without T cell receptor engagement triggers both cytotoxicity and cytokine production in dendritic epidermal T cells[J]. J Invest Dermatol, 2006,126(5):1052-1058. DOI: 10.1038/sj.jid.5700112.
    [25]
    CunninghamTJ,TabacchiM,ElianeJP,et al.Randomized trial of calcipotriol combined with 5-fluorouracil for skin cancer precursor immunotherapy[J].J Clin Invest,2017,127(1):106-116.DOI: 10.1172/JCI89820.
    [26]
    PeterleL,SanfilippoS,BorgiaF,et al.Alopecia areata: a review of the role of oxidative stress, possible biomarkers, and potential novel therapeutic approaches[J].Antioxidants (Basel),2023,12(1):135.DOI: 10.3390/antiox12010135.
    [27]
    XiangJ, QiuMH, ZhangHY. Role of dendritic epidermal T cells in cutaneous carcinoma[J]. Front Immunol, 2020,11:1266. DOI: 10.3389/fimmu.2020.01266.
    [28]
    IbusukiA,KawaiK,YoshidaS,et al.NKG2D triggers cytotoxicity in murine epidermal γδ T cells via PI3K-dependent, Syk/ZAP70-independent signaling pathway[J].J Invest Dermatol,2014,134(2):396-404.DOI: 10.1038/jid.2013.353.
    [29]
    WangYP, BaiY, LiYS, et al. IL-15 enhances activation and IGF-1 production of dendritic epidermal T cells to promote wound healing in diabetic mice[J]. Front Immunol, 2017,8:1557. DOI: 10.3389/fimmu.2017.01557.
    [30]
    Muñoz-RuizM, LlorianM, D'AntuonoR, et al. IFN-γ-dependent interactions between tissue-intrinsic γδ T cells and tissue-infiltrating CD8 T cells limit allergic contact dermatitis[J]. J Allergy Clin Immunol, 2023,152(6):1520-1540. DOI: 10.1016/j.jaci.2023.07.015.
    [31]
    NielsenMM, Dyring-AndersenB, SchmidtJD, et al. NKG2D-dependent activation of dendritic epidermal T cells in contact hypersensitivity[J]. J Invest Dermatol, 2015,135(5):1311-1319. DOI: 10.1038/jid.2015.23.
    • Relative Articles
    • Supplements(0)
    • Cited By
  • 加载中

Catalog

    通讯作者: 陈斌, bchen63@163.com
    • 1. 

      沈阳化工大学材料科学与工程学院 沈阳 110142

    1. 本站搜索
    2. 百度学术搜索
    3. 万方数据库搜索
    4. CNKI搜索

    Figures(4)  / Tables(2)

    Get Citation
    PDF
    XML

    Article Metrics

    Article views (3669) PDF downloads(14) Cited by()
    Proportional views
    Related

    Copyright © Chinese Journal of Burns京ICP备07035254号-14

    E-mail：shaoshangzazhi@163.com

    Website：https://zhsszz.xml-journal.net/

    Supported by: Beijing Renhe Information Technology Co. Ltd    

    /

    DownLoad:  Full-Size Img  PowerPoint
    Return
    Return