TY - JOUR
T1 - Circulating mature dendritic cells homing to the thymus promote thymic epithelial cells involution via the Jagged1/Notch3 axis
AU - Wu, Haojie
AU - Li, Xiaohan
AU - Zhou, Chen
AU - Yu, Qihong
AU - Ge, Shiyao
AU - Pan, Zihui
AU - Zhao, Yangjing
AU - Xia, Sheng
AU - Zhou, Xiaoming
AU - Liu, Xia
AU - Wang, Hui
AU - Shao, Qixiang
N1 - Funding Information:
Haojie Wu, Xiaohan Li, Chen Zhou, and Qihong Yu conducted the experiments. Shiyao Ge, Zihui Pan, and Yangjing Zhao analyzed and interpreted the data. Haojie Wu, Sheng Xia, Xiaoming Zhou, Xia Liu, and Qixiang Shao conceived and designed the experiments. Haojie Wu prepared the manuscript. As funding managers, Hui Wang and Qixiang Shao provided financial support for this study and revised the manuscript. All authors have read and approved the final manuscript.
Publisher Copyright:
© 2021, The Author(s).
PY - 2021/12
Y1 - 2021/12
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=85113875919&partnerID=8YFLogxK
U2 - 10.1038/s41420-021-00619-5
DO - 10.1038/s41420-021-00619-5
M3 - Article
AN - SCOPUS:85113875919
SN - 2058-7716
VL - 7
JO - Cell Death Discovery
JF - Cell Death Discovery
IS - 1
M1 - 225
ER -