title: MHC-compatible bone marrow stromal/stem cells trigger fibrosis by activating host T cells in a scleroderma mouse model.
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.
authors.affiliation: Department of Ophthalmology, Keio University School of Medicine, Tokyo, Japan.
authors.forename: Yoko
authors.initials: Y
authors.lastname: Ogawa
authors.affiliation: Department of Dentistry and Oral Surgery, Keio University School of Medicine, Tokyo, Japan.|Department of Physiology, Keio University School of Medicine, Tokyo, Japan.
authors.forename: Satoru
authors.initials: S
authors.lastname: Morikawa
authors.affiliation: Department of Physiology, Keio University School of Medicine, Tokyo, Japan.
authors.forename: Hideyuki
authors.initials: H
authors.lastname: Okano
authors.affiliation: Department of Physiology, Keio University School of Medicine, Tokyo, Japan.|Department of Biochemistry and Biophysics, Graduate School of Health Care Sciences, Tokyo Medical and Dental University, Tokyo, Japan.
authors.forename: Yo
authors.initials: Y
authors.lastname: Mabuchi
authors.affiliation: Department of Physiology, Keio University School of Medicine, Tokyo, Japan.
authors.forename: Sadafumi
authors.initials: S
authors.lastname: Suzuki
authors.affiliation: Division of Cellular Signaling, Institute for Advanced Medical Research, Keio University School of Medicine, Tokyo, Japan.
authors.forename: Tomonori
authors.initials: T
authors.lastname: Yaguchi
authors.affiliation: Department of Physiology, Keio University School of Medicine, Tokyo, Japan.|Department of Emergency and Critical Care Medicine, Keio University School of Medicine, Tokyo, Japan.
authors.forename: Yukio
authors.initials: Y
authors.lastname: Sato
authors.affiliation: Department of Ophthalmology, Keio University School of Medicine, Tokyo, Japan.
authors.forename: Shin
authors.initials: S
authors.lastname: Mukai
authors.affiliation: Department of Ophthalmology, Keio University School of Medicine, Tokyo, Japan.
authors.forename: Saori
authors.initials: S
authors.lastname: Yaguchi
authors.affiliation: Department of Ophthalmology, Keio University School of Medicine, Tokyo, Japan.
authors.forename: Takaaki
authors.initials: T
authors.lastname: Inaba
authors.affiliation: Division of Hematology, Department of Internal Medicine, Keio University School of Medicine, Tokyo, Japan.
authors.forename: Shinichiro
authors.initials: S
authors.lastname: Okamoto
authors.affiliation: Division of Cellular Signaling, Institute for Advanced Medical Research, Keio University School of Medicine, Tokyo, Japan.
authors.forename: Yutaka
authors.initials: Y
authors.lastname: Kawakami
authors.affiliation: Department of Ophthalmology, Keio University School of Medicine, Tokyo, Japan.
authors.forename: Kazuo
authors.initials: K
authors.lastname: Tsubota
authors.affiliation: Department of Life Science Laboratory of Tumor Biology, Faculty of Medicine, Shimane University, Izumo, Japan.
authors.forename: Yumi
authors.initials: Y
authors.lastname: Matsuzaki
authors.affiliation: Department of Ophthalmology, Keio University School of Medicine, Tokyo, Japan.
authors.forename: Shigeto
authors.initials: S
authors.lastname: Shimmura
mesh_terms: D000818:Animals; D001853:Bone Marrow / Q000473:pathology*; D016026:Bone Marrow Transplantation / Q000009:adverse effects*; D004195:Disease Models, Animal; D005355:Fibrosis / Q000473:pathology*; D051379:Mice; D045743:Scleroderma, Diffuse / Q000473:pathology*; D013234:Stem Cells / Q000276:immunology*; D017154:Stromal Cells / Q000276:immunology*; D013601:T-Lymphocytes / Q000276:immunology*
keywords: adoptive transfer; auto-reactive T cells; autoimmune response/disease; developmental biology; dry eye disease; fibrosis; immunology; mesenchymal stem cells; mouse; stem cells
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