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Elife. 2016 Jan 26;5:e09394. doi: 10.7554/eLife.09394.

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

Author information

1
Department of Ophthalmology, Keio University School of Medicine, Tokyo, Japan.
2
Department of Dentistry and Oral Surgery, Keio University School of Medicine, Tokyo, Japan.
3
Department of Physiology, Keio University School of Medicine, Tokyo, Japan.
4
Department of Biochemistry and Biophysics, Graduate School of Health Care Sciences, Tokyo Medical and Dental University, Tokyo, Japan.
5
Division of Cellular Signaling, Institute for Advanced Medical Research, Keio University School of Medicine, Tokyo, Japan.
6
Department of Emergency and Critical Care Medicine, Keio University School of Medicine, Tokyo, Japan.
7
Division of Hematology, Department of Internal Medicine, Keio University School of Medicine, Tokyo, Japan.
8
Department of Life Science Laboratory of Tumor Biology, Faculty of Medicine, Shimane University, Izumo, Japan.

Abstract

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.

KEYWORDS:

adoptive transfer; auto-reactive T cells; autoimmune response/disease; developmental biology; dry eye disease; fibrosis; immunology; mesenchymal stem cells; mouse; stem cells

PMID:
26809474
PMCID:
PMC4739756
DOI:
10.7554/eLife.09394
[Indexed for MEDLINE]
Free PMC Article

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