4.6 Article

Circulating mature dendritic cells homing to the thymus promote thymic epithelial cells involution via the Jagged1/Notch3 axis

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CELL DEATH DISCOVERY
卷 7, 期 1, 页码 -

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SPRINGERNATURE
DOI: 10.1038/s41420-021-00619-5

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  1. National Natural Science Foundation of China [81671541, 81273202, 81701545, 82071738]
  2. Clinical Medicine Science & Technology Project of Jiangsu Province of China [BL2013024]

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In inflammatory conditions such as chemotherapy and microbial infections, mature dendritic cells (mDCs) can migrate into the thymus and inhibit the proliferation of thymic epithelial cells (TECs) by activating the Jagged1/Notch3 signaling pathway, leading to acute atrophy of the thymus. This process can be reversed by a gamma-secretase inhibitor, suggesting that thymus degeneration can be induced by mass migration or constant homing of mDCs.
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 gamma-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.

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