MHC-compatible bone marrow stromal/stem cells trigger fibrosis by activating host T cells in a scleroderma mouse model

eLife

Tomonori Yaguchi¹  Takaaki Inaba²  Hideyuki Okano³  Satoru Morikawa⁴  Yoko Ogawa⁵  Yutaka Kawakami⁵  Shinichiro Okamoto⁵  Kazuo Tsubota⁵  Yo Mabuchi⁶  Sadafumi Suzuki⁶  Saori Yaguchi⁶  Yukio Sato⁶  Shigeto Shimmura⁷  Shin Mukai⁷  Yumi Matsuzaki⁸ 

[1] Department of Biochemistry and Biophysics, Graduate School of Health Care Sciences, Tokyo Medical and Dental University, Tokyo, Japan;Department of Emergency and Critical Care Medicine, Keio University School of Medicine, Tokyo, Japan;Department of Physiology, Keio University School of Medicine, Tokyo, Japan;Department of Dentistry and Oral Surgery, Keio University School of Medicine, Tokyo, Japan;Department of Ophthalmology, Keio University School of Medicine, Tokyo, Japan;Department of Physiology, Keio University School of Medicine, Tokyo, Japan;Division of Cellular Signaling, Institute for Advanced Medical Research, Keio University School of Medicine, Tokyo, Japan;Division of Hematology, Department of Internal Medicine, Keio University School of Medicine, Tokyo, Japan;

关键词: mesenchymal stem cell;    autoimmune response/disease;    fibrosis;    dry eye disease;    adoptive transfer;    auto-reactive T cells;   

DOI  :  10.7554/eLife.09394

来源: DOAJ

【 摘 要 】

Fibrosis of organs is observed in systemic autoimmune disease. Using a scleroderma mouse, we show that transplantation of MHC compatible, minor antigen mismatched bone marrow stromal/stem cells (BMSCs) play a role in the pathogenesis of fibrosis. Removal of donor BMSCs rescued mice from disease. Freshly isolated PDGFRα+ Sca-1+ BMSCs expressed MHC class II following transplantation and activated host T cells. A decrease in FOXP3+ CD25+ Treg population was observed. T cells proliferated and secreted IL-6 when stimulated with mismatched BMSCs in vitro. Donor T cells were not involved in fibrosis because transplanting T cell-deficient RAG2 knock out mice bone marrow still caused disease. Once initially triggered by mismatched BMSCs, the autoimmune phenotype was not donor BMSC dependent as the phenotype was observed after effector T cells were adoptively transferred into naïve syngeneic mice. Our data suggest that minor antigen mismatched BMSCs trigger systemic fibrosis in this autoimmune scleroderma model.

【 授权许可】

Unknown