MHC-compatible bone marrow stromal/stem cells trigger fibrosis by activating host T cells in a scleroderma mouse model
| Autor: | Shinichiro Okamoto, Kazuo Tsubota, Yumi Matsuzaki, Yoko Ogawa, Takaaki Inaba, Saori Yaguchi, Shin Mukai, Tomonori Yaguchi, Satoru Morikawa, Yo Mabuchi, Yutaka Kawakami, Sadafumi Suzuki, Hideyuki Okano, Shigeto Shimmura, Yukio Sato |
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| Rok vydání: | 2015 |
| Předmět: |
0301 basic medicine
Stromal cell adoptive transfer Mouse QH301-705.5 Science T-Lymphocytes Immunology Clinical uses of mesenchymal stem cells Biology General Biochemistry Genetics and Molecular Biology 03 medical and health sciences Mice 0302 clinical medicine Antigen stomatognathic system Bone Marrow medicine Animals IL-2 receptor Biology (General) mesenchymal stem cell Bone Marrow Transplantation MHC class II auto-reactive T cells General Immunology and Microbiology General Neuroscience Stem Cells fibrosis autoimmune response/disease FOXP3 hemic and immune systems General Medicine dry eye disease Disease Models Animal 030104 developmental biology medicine.anatomical_structure Developmental Biology and Stem Cells 030220 oncology & carcinogenesis Scleroderma Diffuse biology.protein Medicine Bone marrow Stem cell Stromal Cells Research Article |
| Zdroj: | eLife eLife, Vol 5 (2016) |
| ISSN: | 2050-084X |
| Popis: | 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. DOI: http://dx.doi.org/10.7554/eLife.09394.001 eLife digest Systemic scleroderma is an autoimmune disease caused by the immune system attacking the body’s connective tissues, which provide the body with structural support. Immune cells called T cells accumulate in connective tissue, which leads to the hardening of the skin and may also damage the heart, lungs and other internal organs. However, it is not clear what prompts the T cells to accumulate in the connective tissues of these individuals. Autoimmune diseases develop when the immune system mistakenly identifies host cells as being a threat to the body. Normally, the immune system recognizes healthy body cells by the presence of particular proteins on the surface of the cells. A set of surface proteins called the major histocompatibility complexes (MHCs) play a major role in this process, but there are also many other surface proteins that play more minor roles. In 2002, researchers developed a method that can trigger the symptoms of systemic scleroderma in mice. This method involves transplanting bone marrow from one mouse into another mouse. Both mice have identical MHC proteins on the surfaces of their cells, but have some differences in other cell surface proteins, and so the bone marrow from the donor mouse triggers an immune response in the recipient. To better understand how this mouse “model” of systemic scleroderma works, Ogawa, Morikawa et al. refined the method so that they could just transplant specific types of bone marrow cells into the recipient mice. The experiments reveal that bone marrow stromal stem cells, but not so-called “hematopoietic stem cells”, from a donor mouse are responsible for triggering the immune response and disease symptoms in the recipients. Ogawa, Morikawa et al.’s findings show that mismatched minor cell surface proteins on bone marrow stromal stem cells can trigger symptoms of systemic scleroderma in mice. Further studies are required to find out how these cells encourage T cells to trigger an autoimmune response. DOI: http://dx.doi.org/10.7554/eLife.09394.002 |
| Databáze: | OpenAIRE |
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