☆ 4.7 Article

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

INTERNATIONAL IMMUNOPHARMACOLOGY (2020)

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期刊

INTERNATIONAL IMMUNOPHARMACOLOGY
卷 84, 期 -, 页码 -

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ELSEVIER
DOI: 10.1016/j.intimp.2020.106541

关键词

Extracellular vesicles; Chronic graft-versus-host-disease; Mesenchymal stem cells; Immunoregulation; Macrophage

类别

Immunology Pharmacology & Pharmacy

资金

  1. National Natural Science Foundation of China [81870121, 81671585, 81500102, 81370665]
  2. Science and Technology Planning Project of Guangdong Province, China [2014B020212009, 2014B020226002, 2015B020227003, 2015B020226001, 2017B020230004]
  3. Science and Technology Planning Project of Guangzhou, China [201803040005, 201803040011, 201400000003-4]
  4. Project of Administration of Traditional Chinese Medicine of Guangdong Province of China [20191008]

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Objective: To illustrate the potential effects and mechanism of extracellular vesicles derived from mesenchymal stem cells (MSC-EVs) on fibrosis in sclerodermatous chronic graft-versus-host-disease (cGVHD) models after allogeneic hematopoietic stem cell transplantation. Methods: We first observed the therapeutic effects of MSC-EVs on a minor histocompatibility haploidentical model of sclerodermatous cGVHD and the function of MSC-EVs on skin fibrosis and macrophage activation and the related pro-fibrosis protein. Additionally, we observed the effects of MSC-EVs on B cells, the T follicular helper cell (TFH) and germinal center B cell (GC B cells) interaction and the ratio of B cell activation factor (BAFF) to B cells in vivo. Results: MSC-EVs treatment could alleviate the cGVHD scores and fibrosis of skin in sclerodermatous cGVHD mice, and this was associated with a reduction macrophage percentage in the skin and spleen, and a reduction in macrophage infiltration and TGF-beta and smad2 production in the skin. Additionally, MSC-EVs influence B cells immune response by blocking the TFH/GC B cells interaction and reducing the ratio of BAFF to B cells in vivo. Conclusion: MSC-EVs prevent the fibrosis of sclerodermatous cGVHD mouse model by suppressing the activation of macrophages and B cells immune response.

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