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. 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. 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). 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.

中文翻译：

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胸腺来源的间充质基质/干细胞的一氧化氮依赖性免疫抑制功能

T 细胞发育和适应性免疫的形成需要胸腺。基质细胞包括胸腺上皮细胞（TEC）和间充质基质细胞（MSC），对于胸腺功能至关重要。然而，胸腺来源的间充质干细胞（T-MSCs）的免疫调节功能尚未得到充分探索。从小鼠胸腺中分离出 MSC，并对其一般特征（包括表面标记和多分化潜能）进行了表征。体外和体内评估了 IFN-γ 和 TNF-α 刺激的 T-MSC 的免疫调节功能。此外，通过使用与各种 MSC 谱系 Cre 重组酶系杂交的 tdTomato-flox 小鼠来询问胸腺中 MSC 的空间分布。T-MSCs 的一个亚群表达 Nestin，主要分布在胸腺髓质区和皮质髓质交界处，但不分布在被膜中。Nestin阳性T-MSC表现出典型的免疫表型特征和分化潜力。此外，当用 IFN-γ 和 TNF-α 刺激时，它们可以像 BM-MSC 一样有效地抑制活化的 T 淋巴细胞，并且这种功能依赖于一氧化氮 (NO) 的产生。此外，T-MSCs在急性肝损伤和炎症性肠病（IBD）方面表现出显着的治疗效果。Nestin阳性MSCs主要分布于胸腺髓质和皮质-髓质交界处，在炎性细胞因子刺激下具有免疫抑制能力。这些发现对于理解胸腺中 MSC 的生理功能具有重要意义。