| First Author | Wang J | Year | 2019 |
| Journal | Int Immunol | Volume | 31 |
| Issue | 3 | Pages | 127-139 |
| PubMed ID | 30534943 | Mgi Jnum | J:276890 |
| Mgi Id | MGI:6315701 | Doi | 10.1093/intimm/dxy073 |
| Citation | Wang J, et al. (2019) Hassall's corpuscles with cellular-senescence features maintain IFNalpha production through neutrophils and pDC activation in the thymus. Int Immunol 31(3):127-139 |
| abstractText | 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 IFNalpha expression required for SP T-cell maturation in the thymic medulla. |
