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

Yoko Ogawa, Satoru Morikawa, Hideyuki Okano, Yo Mabuchi, Sadafumi Suzuki, Tomonori Yaguchi, Yukio Sato, Shin Mukai, Saori Yaguchi, Takaaki Inaba, Shinichiro Okamoto, Yutaka Kawakami, Kazuo Tsubota, Yumi Matsuzaki, Shigeto Shimmura

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15 Citations (Scopus)

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.

Original languageEnglish
Article numbere09394
JournaleLife
Volume5
Issue numberJANUARY2016
DOIs
Publication statusPublished - 2016 Jan 26

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)
  • Immunology and Microbiology(all)
  • Medicine(all)
  • Neuroscience(all)

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    Ogawa, Y., Morikawa, S., Okano, H., Mabuchi, Y., Suzuki, S., Yaguchi, T., Sato, Y., Mukai, S., Yaguchi, S., Inaba, T., Okamoto, S., Kawakami, Y., Tsubota, K., Matsuzaki, Y., & Shimmura, S. (2016). MHC-compatible bone marrow stromal/stem cells trigger fibrosis by activating host T cells in a scleroderma mouse model. eLife, 5(JANUARY2016), [e09394]. https://doi.org/10.7554/eLife.09394