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Publication : Nitric oxide-dependent immunosuppressive function of thymus-derived mesenchymal stromal/stem cells.

First Author  Su X Year  2023
Journal  Biol Direct Volume  18
Issue  1 Pages  59
PubMed ID  37723551 Mgi Jnum  J:358287
Mgi Id  MGI:7778524 Doi  10.1186/s13062-023-00415-4
Citation  Su X, et al. (2023) Nitric oxide-dependent immunosuppressive function of thymus-derived mesenchymal stromal/stem cells. Biol Direct 18(1):59
abstractText  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-gamma and TNF-alpha 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-gamma and TNF-alpha, 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.
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