Establishment of a mouse model of skin-dominant chronic graft-versus-host disease

Weihao WANG; Shijie YANG; Yuxuan DU; Xiaoqi WANG; Tao HONG; Yundi HE; Rui WANG; Chao MA; Huihui AN; Junjie WANG; Yunfang ZHANG; Qiangguo GAO; Xi ZHANG

doi:10.16016/j.1000-5404.202108060

您当前的位置：

首页 >

文章列表页 >

Establishment of a mouse model of skin-dominant chronic graft-versus-host disease

Monographic Reports: Basic and clinical research on complications after hematopoietic stem cell transplantation | 更新时间：2026-01-09

- Establishment of a mouse model of skin-dominant chronic graft-versus-host disease
- Journal of Third Military Medical University Vol. 43, Issue 21, Pages: 2286-2293(2021)
- 作者机构：
  
  1.400037 重庆，陆军军医大学(第三军医大学)第二附属医院血液病医学中心，全军血液病中心，创伤、烧伤与复合伤国家重点实验室
  2.563099 贵州遵义，遵义医科大学第二附属医院检验科
  3.400038 重庆，陆军军医大学(第三军医大学)基础医学院细胞生物学教研室
- 作者简介：
- 基金信息：
  
  the Key Special Project of National Key R & D Program(2017YFA0105502);the 2020 Open Project of National Clinical Medicine Research Center for Hematological System Diseases(2020ZKZC02);the Special Project of Basic Frontier of Military Medicine(2018YQYLY002)
- DOI：10.16016/j.1000-5404.202108060
  CLC： R-332;R617;R733.7
- Received：10 August 2021，
  
  Revised：2021-09-05，
  
  Published：15 November 2021
- 稿件说明：
移动端阅览
Weihao WANG, Shijie YANG, Yuxuan DU, et al. Establishment of a mouse model of skin-dominant chronic graft-versus-host disease[J]. Journal of Third Military Medical University, 2021, 43(21): 2286-2293.
DOI：

Weihao WANG, Shijie YANG, Yuxuan DU, et al. Establishment of a mouse model of skin-dominant chronic graft-versus-host disease[J]. Journal of Third Military Medical University, 2021, 43(21): 2286-2293. DOI： 10.16016/j.1000-5404.202108060.

摘要

目的

构建皮肤优势型慢性移植物抗宿主病(chronic graft-versus-host disease

cGVHD)小鼠模型。

方法

利用致死剂量辐照BALB/c小鼠，并接受来自B10.D2供鼠混合的骨髓细胞和脾脏细胞以构建皮肤优势型cGVHD小鼠模型，通过小鼠临床表现、病理特征及靶器官细胞亚群评估模型构建情况。

结果

模型小鼠的临床表现以皮肤脱毛、硬化、皮屑、结痂和由皮肤皱缩硬化引起的弓背和关节僵直为主，临床病理评分随疾病进展升高，但无明显肠道cGVHD表现。病理改变中皮肤出现明显胶原沉积，毛囊减少甚至消失，而其他靶器官病理改变不明显。对以上靶器官行T细胞亚群分析，发现Th1细胞、CD4

IL-13

T细胞和Tc1细胞与疾病进展密切。

结论

成功构建可用于实验研究的皮肤优势型小鼠cGVHD模型，病理变化主要以皮肤纤维化表现为主。

Abstract

Objective

To construct a mouse model of skin-dominant chronic graft-versus-host disease (cGVHD).

Methods

BALB/c mice were irradiated with lethal dose and then received a mixture of bone marrow and spleen cells transplantation from B10.D2 donor mice. Then the clinical manifestations

pathological features of the mice and cell subsets of targeted organs were observed to evaluate the establishment of model.

Results

The clinical manifestations of the model mice mainly involved skin depilation

sclerosis

dandruff

scab

as well as arched back and joint stiffness due to skin shrinkage and

sclerosis. The clinicopathological scores were increased with the progression of cGVHD

while the model mice showed no obvious manifestations of intestinal cGVHD. Moreover

increase of collagen deposition and decrease or even disappearance of hair follicles was observed on the histopathologic sections of skin

while other targeted organs showed no major alterations. T cell subsets analysis indicated that Th1 cells

CD4

IL-13

T cells and Tc1 cells were closely related to the disease progression.

Conclusion

The skin-dominant cGVHD mouse model is successfully established

with skin damage and fibrosis as main pathological changes.

关键词

Keywords

references

KRÖGER N. Preventing graft-versus-host disease without losing graft-versus-leukemia effect after allogeneic stem-cell transplantation[J]. J Clin Oncol, 2020, 38(29): 3357-3360. DOI: 10.1200/jco.20.01756.

中华医学会血液学分会造血干细胞应用学组, 中国抗癌协会血液病转化委员会. 慢性移植物抗宿主病(cGVHD)诊断与治疗中国专家共识(2021年版)[J]. 中华血液学杂志, 2021, 42(4): 265-275.

Applied Hematopoietic Stem Cell Group of Hematology Branch of Chinese Medical Association, Hematological Diseases Transformation Committee of Chinese Anti-Cancer Society. Chinese expert consensus on diagnosis and treatment of chronic graft-versus-host disease (cGVHD) (2021 edition)[J]. Chin J Hematol, 2021, 42(4): 265-275.

陈婷, 李小平, 高强国, 等. 不同方法检测急性移植物抗宿主病患者的血清标志物[J]. 第三军医大学学报, 2019, 41(23): 2280-2284. DOI: 10.16016/j.1000-5404.201907252.

CHEN T, LI X P, GAO Q G, et al . Different methods for detecting serum markers in patients with acute graft versus host disease[J ] . J Third Mil Med Univ, 2019, 41(23): 2280-2284. DOI: 10.16016/j.1000-5404.201907252.

HOGENES M C H, VAN DORP S, VAN KUIK J, et al . Modifying graft-versus-host disease in a humanized mouse model by targeting macrophages or B-cells[J ] . J Immunol Res, 2019, 2019: 3538963. DOI: 10.1155/2019/3538963.

YE Y, RICARD L, STOCKER N, et al . A novel mouse model of acute graft-versus-host disease based on chemotherapy conditioning and G-CSF mobilized graft[J ] . Bone Marrow Transplant, 2020, 55(3): 570-577. DOI: 10.1038/s41409-019-0700-4.

MVLLER A M S, MIN D, WERNIG G, et al . Modeling chronic graft-versus-host disease in MHC-matched mouse strains: genetics, graft composition, and tissue targets[J ] . Biol Blood Marrow Transplant, 2019, 25(12): 2338-2349. DOI: 10.1016/j.bbmt.2019.08.001.

SCHROEDER M A, DIPERSIO J F. Mouse models of graft-versus-host disease: advances and limitations[J]. Dis Model Mech, 2011, 4(3): 318-333. DOI: 10.1242/dmm.006668.

BOIERI M, SHAH P, JALAPOTHU D, et al . Rat acute GvHD is Th1 driven and characterized by predominant donor CD4 + T-cell infiltration of skin and gut[J ] . Exp Hematol, 2017, 50: 33-45. e3. DOI: 10.1016/j.exphem.2017.02.002..

MALARD F, BOSSARD C, ARBEZ J, et al . Plasmacytoid dendritic cells (PDC) and Th17 immune response contribution in gut acute graft-versus-host-disease (GVHD)[J ] . Blood, 2011, 118(21): 2968. DOI: 10.1182/blood.V118.21.2968.2968.

GUO L Y, LAI P L, WANG Y L, et al . Extracellular vesicles derived from mesenchymal stem cells prevent skin fibrosis in the cGVHD mouse model by suppressing the activation of macrophages and B cells immune response[J ] . Int Immunopharmacol, 2020, 84: 106541. DOI: 10.1016/j.intimp.2020.106541.

KAPLAN D H, ANDERSON B E, MCNIFF J M, et al . Target antigens determine graft-versus-host disease phenotype[J ] . J Immunol, 2004, 173(9): 5467-5475. DOI: 10.4049/jimmunol.173.9.5467.

PAN B, WANG D, LI L, et al . IL-22 accelerates Thymus regeneration via Stat3/mcl-1 and decreases chronic graft-versus-host disease in mice after allotransplants[J ] . Biol Blood Marrow Transplant, 2019, 25(10): 1911-1919. DOI: 10.1016/j.bbmt.2019.06.002.

FURUE K, ITO T, TSUJI G, et al . The IL-13-OVOL1-FLG axis in atopic dermatitis[J ] . Immunology, 2019, 158(4): 281-286. DOI: 10.1111/imm.13120.

BODOOR K, AL-QARQAZ F, HEIS L A, et al . IL-33/13 axis and IL-4/31 axis play distinct roles in inflammatory process and itch in psoriasis and atopic dermatitis[J ] . Clin Cosmet Investig Dermatol, 2020, 13: 419-424. DOI: 10.2147/ccid.s257647.

ODAK I, DEPKAT-JAKOB A, BECK M, et al . Donor-derived IL-17A and IL-17F deficiency triggers Th1 allo-responses and increases gut leakage during acute GVHD[J ] . PLoS ONE, 2020, 15(4): e0231222. DOI: 10.1371/journal.pone.0231222.

MORIN F, KAVIAN N, MARUT W, et al . Inhibition of EGFR tyrosine kinase by erlotinib prevents sclerodermatous graft-versus-host disease in a mouse model[J ] . J Invest Dermatol, 2015, 135(10): 2385-2393. DOI: 10.1038/jid.2015.174.

YEH S P, LIAO Y M, LO W J, et al . Kinetics of T helper subsets and associated cytokines correlate well with the clinical activity of graft-versus-host disease[J ] . PLoS ONE, 2012, 7(9): e44416. DOI: 10.1371/journal.pone.0044416.

TAWARA I, NIEVES E, LIU C, et al . Host basophils are dispensable for induction of donor T helper 2 cell differentiation and severity of experimental graft-versus-host disease[J ] . Biol Blood Marrow Transplant, 2011, 17(12): 1747-1753. DOI: 10.1016/j.bbmt.2011.08.013.

LEE G R. The balance of Th17 versus treg cells in autoimmunity[J]. Int J Mol Sci, 2018, 19(3): 730. DOI: 10.3390/ijms19030730.

YASUDA K, TAKEUCHI Y, HIROTA K. The pathogenicity of Th17 cells in autoimmune diseases[J]. Semin Immunopathol, 2019, 41(3): 283-297. DOI: 10.1007/s00281-019-00733-8.

DELENS L, EHX G, SOMJA J, et al . In vitro Th17-polarized human CD4 + T cells exacerbate xenogeneic graft-versus-host disease[J ] . Biol Blood Marrow Transplant, 2019, 25(2): 204-215. DOI: 10.1016/j.bbmt.2018.10.007..

GUTIÉRREZ-HOYA A, LÓPEZ-SANTIAGO R, VELA-OJEDA J, et al . Role of CD8 regulatory T cells versus Tc1 and Tc17 cells in the development of human graft-versus-host disease[J ] . J Immunol Res, 2017, 2017: 1236219. DOI: 10.1155/2017/1236219.

CHASSET F, LE BUANEC H, SICRE DE FONTBRUNE F, et al . Evidence of Th1, Th17 and Tc17 cells in psoriasiform chronic graft-versus-host disease[J ] . Exp Dermatol, 2016, 25(1): 64-65. DOI:10.1111/exd.12857.

Views

下载量

CSCD

Alert me when the article has been cited

提交

Tools

Publicity Resources

Role of autophagy during cutaneous wound healing in mice

Expression profile of AQP9 in liver of rats with type 2 diabetes mellitus

A combined strategy of surface markers for sorting immune cell subsets in patients with chronic graft-versus-host disease

NLRP3 inflammasome activation mediates terahertz exposure-induced skin aseptic inflammation in mice

Related Author

Na ZHAO

Dengqun LIU

Guojian WANG

Shuang LONG

Huimin WAN

Yongping SU

Tao WANG

Yuan LI

Related Institution

State Key Laboratory of Trauma, Burns and Combined Injury, Department of Anti-radiation Medicine, Chongqing Engineering Research Center for Nanomedicine, Institute of Combined Injury, Faculty of Preventive Military Medicine, Army Medical University (Third Military Medical University)

Neuroscience Center, Chongqing Medical University

Seven-year Training Group of Grade 2013, First Clinical College of Chongqing Medical University

⁰