期刊
INTERNATIONAL IMMUNOLOGY
卷 31, 期 3, 页码 127-139出版社
OXFORD UNIV PRESS
DOI: 10.1093/intimm/dxy073
关键词
Hassall's bodies; cell senescence; type I interferon; mTEC; thymic epithelial cells
类别
资金
- Japanese Ministry of Education, Culture, Science, Sports, and Technology [24590580, 15H01154, 17H05641, 18H02640, 18K19442, 24111008]
- Japan Agency for Medical Research and Development [JP18gm5010001]
- iPS Cell Research Fund
- Takeda Science Foundation
- Grants-in-Aid for Scientific Research [17H05641, 18K19442, 18H02640, 24590580, 15H01154, 24111008] Funding Source: KAKEN
Hassall's corpuscles (HCs) are composed of cornifying, terminally differentiated medullary thymic epithelial cells (mTECs) that are developed under the control of Aire. Here, we demonstrated that HC-mTECs show features of cellular senescence and produce inflammatory cytokines and chemokines including CXCL5, thereby recruiting and activating neutrophils to produce IL-23 in the thymic medulla. We further indicated that thymic plasmacytoid dendritic cells (pDCs) expressing IL-23 receptors constitutively produced Ifna, which plays a role in single positive (SP) cell maturation, in an Il23a-dependent manner. Neutrophil depletion with anti-Ly6G antibody injection resulted in a significant decrease of Ifna expression in the thymic pDCs, suggesting that thymic neutrophil activation underlies the Ifna expression in thymic pDCs in steady state conditions. A New Zealand White mouse strain showing HC hyperplasia exhibited greater numbers and activation of thymic neutrophils and pDCs than B6 mice, whereas Aire-deficient B6 mice with defective HC development and SP thymocyte maturation showed significantly compromised numbers and activation of these cells. These results collectively suggested that HC-mTECs with cell-senescence features initiate a unique cell activation cascade including neutrophils and pDCs leading to the constitutive IFN expression required for SP T-cell maturation in the thymic medulla.
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