Multiple proinflammatory conditions, including chemotherapy, radiotherapy, transplant rejection, and microbial infections, have been identified to induce involution of the thymus. However, the underlying cellular and molecular mechanisms of these inflammatory conditions inducing apoptosis of thymic epithelial cells (TECs), the main components of the thymus, remain largely unknown. In the circulation, mature dendritic cells (mDCs), the predominant initiator of innate and adaptive immune response, can migrate into the thymus. Herein, we demonstrated that mDCs were able to directly inhibit TECs proliferation and induce their apoptosis by activating the Jagged1/Notch3 signaling pathway. Intrathymic injection of either mDCs or recombinant mouse Jagged1-human Fc fusion protein (rmJagged1-hFc) into mice resulted in acute atrophy of the thymus. Furthermore, DAPT, a γ-secretase inhibitor, reversed the effects induced by mDC or rmJagged1-hFc. These findings suggest that acute or aging-related thymus degeneration can be induced either by mass migration of circulating mDCs in a short period of time or by a few but constantly homing mDCs.

多种促炎性疾病，包括化疗、放疗、移植排斥和微生物感染，已被确定可诱导胸腺复旧。然而，这些炎症条件诱导胸腺上皮细胞（TEC）（胸腺的主要成分）凋亡的潜在细胞和分子机制仍然很大程度上未知。在循环中，成熟的树突状细胞（mDC）是先天性和适应性免疫反应的主要引发剂，可以迁移到胸腺中。在此，我们证明 mDC 能够通过激活 Jagged1/Notch3 信号通路直接抑制 TEC 增殖并诱导其凋亡。将 mDC 或重组小鼠 Jagged1-人 Fc 融合蛋白 (rmJagged1-hFc) 胸腺内注射到小鼠体内会导致胸腺急性萎缩。此外，DAPT（一种 γ 分泌酶抑制剂）可逆转 mDC 或 rmJagged1-hFc 诱导的作用。这些发现表明，急性或与衰老相关的胸腺变性可以由循环 mDC 在短时间内的大量迁移或少数但不断归巢的 mDC 引起。