Nitric oxide-dependent immunosuppressive function of thymus-derived mesenchymal stromal/stem cells
Abstract Background The thymus is required for T cell development and the formation of the adaptive immunity. Stromal cells, which include thymic epithelial cells (TECs) and mesenchymal stromal cells (MSCs), are essential for thymic function. However, the immunomodulatory function of thymus-derived...
| Main Authors: | , , , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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BMC
2023-09-01
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| Series: | Biology Direct |
| Subjects: | |
| Online Access: | https://doi.org/10.1186/s13062-023-00415-4 |
| _version_ | 1827635239968571392 |
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| author | Xiao Su Xiaolei Li Shiqing Wang Xiaotong Xue Rui Liu Xiaojing Bai Pixia Gong Chao Feng Lijuan Cao Tingting Wang Yayun Ding Junjie Jiang Yongjing Chen Yufang Shi Changshun Shao |
| author_facet | Xiao Su Xiaolei Li Shiqing Wang Xiaotong Xue Rui Liu Xiaojing Bai Pixia Gong Chao Feng Lijuan Cao Tingting Wang Yayun Ding Junjie Jiang Yongjing Chen Yufang Shi Changshun Shao |
| author_sort | Xiao Su |
| collection | DOAJ |
| description | Abstract Background The thymus is required for T cell development and the formation of the adaptive immunity. Stromal cells, which include thymic epithelial cells (TECs) and mesenchymal stromal cells (MSCs), are essential for thymic function. However, the immunomodulatory function of thymus-derived MSCs (T-MSCs) has not been fully explored. Methods MSCs were isolated from mouse thymus and their general characteristics including surface markers and multi-differentiation potential were characterized. The immunomodulatory function of T-MSCs stimulated by IFN-γ and TNF-α was evaluated in vitro and in vivo. Furthermore, the spatial distribution of MSCs in the thymus was interrogated by using tdTomato-flox mice corssed to various MSC lineage Cre recombinase lines. Results A subset of T-MSCs express Nestin, and are mainly distributed in the thymic medulla region and cortical-medulla junction, but not in the capsule. The Nestin-positive T-MSCs exhibit typical immunophenotypic characteristics and differentiation potential. Additionally, when stimulated with IFN-γ and TNF-α, they can inhibit activated T lymphocytes as efficiently as BM-MSCs, and this function is dependent on the production of nitric oxide (NO). Additionally, the T-MSCs exhibit a remarkable therapeutic efficacy in acute liver injury and inflammatory bowel disease (IBD). Conclusions Nestin-positive MSCs are mainly distributed in medulla and cortical-medulla junction in thymus and possess immunosuppressive ability upon stimulation by inflammatory cytokines. The findings have implications in understanding the physiological function of MSCs in thymus. |
| first_indexed | 2024-03-09T15:25:08Z |
| format | Article |
| id | doaj.art-312c5c52a0f84768b3af816afab9b34e |
| institution | Directory Open Access Journal |
| issn | 1745-6150 |
| language | English |
| last_indexed | 2024-03-09T15:25:08Z |
| publishDate | 2023-09-01 |
| publisher | BMC |
| record_format | Article |
| series | Biology Direct |
| spelling | doaj.art-312c5c52a0f84768b3af816afab9b34e2023-11-26T12:34:35ZengBMCBiology Direct1745-61502023-09-0118111510.1186/s13062-023-00415-4Nitric oxide-dependent immunosuppressive function of thymus-derived mesenchymal stromal/stem cellsXiao Su0Xiaolei Li1Shiqing Wang2Xiaotong Xue3Rui Liu4Xiaojing Bai5Pixia Gong6Chao Feng7Lijuan Cao8Tingting Wang9Yayun Ding10Junjie Jiang11Yongjing Chen12Yufang Shi13Changshun Shao14First Affiliated Hospital of Soochow University, State Key Laboratory of Radiation Medicine and Protection, Institutes for Translational Medicine, Soochow University Suzhou Medical CollegeFirst Affiliated Hospital of Soochow University, State Key Laboratory of Radiation Medicine and Protection, Institutes for Translational Medicine, Soochow University Suzhou Medical CollegeFirst Affiliated Hospital of Soochow University, State Key Laboratory of Radiation Medicine and Protection, Institutes for Translational Medicine, Soochow University Suzhou Medical CollegeFirst Affiliated Hospital of Soochow University, State Key Laboratory of Radiation Medicine and Protection, Institutes for Translational Medicine, Soochow University Suzhou Medical CollegeFirst Affiliated Hospital of Soochow University, State Key Laboratory of Radiation Medicine and Protection, Institutes for Translational Medicine, Soochow University Suzhou Medical CollegeFirst Affiliated Hospital of Soochow University, State Key Laboratory of Radiation Medicine and Protection, Institutes for Translational Medicine, Soochow University Suzhou Medical CollegeFirst Affiliated Hospital of Soochow University, State Key Laboratory of Radiation Medicine and Protection, Institutes for Translational Medicine, Soochow University Suzhou Medical CollegeFirst Affiliated Hospital of Soochow University, State Key Laboratory of Radiation Medicine and Protection, Institutes for Translational Medicine, Soochow University Suzhou Medical CollegeFirst Affiliated Hospital of Soochow University, State Key Laboratory of Radiation Medicine and Protection, Institutes for Translational Medicine, Soochow University Suzhou Medical CollegeFirst Affiliated Hospital of Soochow University, State Key Laboratory of Radiation Medicine and Protection, Institutes for Translational Medicine, Soochow University Suzhou Medical CollegeFirst Affiliated Hospital of Soochow University, State Key Laboratory of Radiation Medicine and Protection, Institutes for Translational Medicine, Soochow University Suzhou Medical CollegeFirst Affiliated Hospital of Soochow University, State Key Laboratory of Radiation Medicine and Protection, Institutes for Translational Medicine, Soochow University Suzhou Medical CollegeFirst Affiliated Hospital of Soochow University, State Key Laboratory of Radiation Medicine and Protection, Institutes for Translational Medicine, Soochow University Suzhou Medical CollegeFirst Affiliated Hospital of Soochow University, State Key Laboratory of Radiation Medicine and Protection, Institutes for Translational Medicine, Soochow University Suzhou Medical CollegeFirst Affiliated Hospital of Soochow University, State Key Laboratory of Radiation Medicine and Protection, Institutes for Translational Medicine, Soochow University Suzhou Medical CollegeAbstract Background The thymus is required for T cell development and the formation of the adaptive immunity. Stromal cells, which include thymic epithelial cells (TECs) and mesenchymal stromal cells (MSCs), are essential for thymic function. However, the immunomodulatory function of thymus-derived MSCs (T-MSCs) has not been fully explored. Methods MSCs were isolated from mouse thymus and their general characteristics including surface markers and multi-differentiation potential were characterized. The immunomodulatory function of T-MSCs stimulated by IFN-γ and TNF-α was evaluated in vitro and in vivo. Furthermore, the spatial distribution of MSCs in the thymus was interrogated by using tdTomato-flox mice corssed to various MSC lineage Cre recombinase lines. Results A subset of T-MSCs express Nestin, and are mainly distributed in the thymic medulla region and cortical-medulla junction, but not in the capsule. The Nestin-positive T-MSCs exhibit typical immunophenotypic characteristics and differentiation potential. Additionally, when stimulated with IFN-γ and TNF-α, they can inhibit activated T lymphocytes as efficiently as BM-MSCs, and this function is dependent on the production of nitric oxide (NO). Additionally, the T-MSCs exhibit a remarkable therapeutic efficacy in acute liver injury and inflammatory bowel disease (IBD). Conclusions Nestin-positive MSCs are mainly distributed in medulla and cortical-medulla junction in thymus and possess immunosuppressive ability upon stimulation by inflammatory cytokines. The findings have implications in understanding the physiological function of MSCs in thymus.https://doi.org/10.1186/s13062-023-00415-4ThymusMesenchymal stromal/stem cellsImmunomodulationNONestin |
| spellingShingle | Xiao Su Xiaolei Li Shiqing Wang Xiaotong Xue Rui Liu Xiaojing Bai Pixia Gong Chao Feng Lijuan Cao Tingting Wang Yayun Ding Junjie Jiang Yongjing Chen Yufang Shi Changshun Shao Nitric oxide-dependent immunosuppressive function of thymus-derived mesenchymal stromal/stem cells Biology Direct Thymus Mesenchymal stromal/stem cells Immunomodulation NO Nestin |
| title | Nitric oxide-dependent immunosuppressive function of thymus-derived mesenchymal stromal/stem cells |
| title_full | Nitric oxide-dependent immunosuppressive function of thymus-derived mesenchymal stromal/stem cells |
| title_fullStr | Nitric oxide-dependent immunosuppressive function of thymus-derived mesenchymal stromal/stem cells |
| title_full_unstemmed | Nitric oxide-dependent immunosuppressive function of thymus-derived mesenchymal stromal/stem cells |
| title_short | Nitric oxide-dependent immunosuppressive function of thymus-derived mesenchymal stromal/stem cells |
| title_sort | nitric oxide dependent immunosuppressive function of thymus derived mesenchymal stromal stem cells |
| topic | Thymus Mesenchymal stromal/stem cells Immunomodulation NO Nestin |
| url | https://doi.org/10.1186/s13062-023-00415-4 |
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