Post-Aire Medullary Thymic Epithelial Cells and Hassall’s Corpuscles as Inducers of Tonic Pro-Inflammatory Microenvironment

Frontiers in Immunology

Ahto Salumets¹  Hedi Peterson¹  Martti Laan²  Rudolf Bichele²  Kerli Reintamm²  Annabel Klein²  Pärt Peterson² 

[1] Institute of Computer Science, Faculty of Science and Technology, University of Tartu, Tartu, Estonia;Molecular Pathology Research Group, Institute of Biomedicine and Translational Medicine, University of Tartu, Tartu, Estonia;

关键词: Hassall’s corpuscles;    medullary thymic epithelial cells;    AIRE;    thymus;    central tolerance;    S100A8;   

DOI  :  10.3389/fimmu.2021.635569

来源: DOAJ

【 摘 要 】

While there is convincing evidence on the role of Aire-positive medullary thymic epithelial cells (mTEC) in the induction of central tolerance, the nature and function of post-Aire mTECs and Hassall’s corpuscles have remained enigmatic. Here we summarize the existing data on these late stages of mTEC differentiation with special focus on their potential to contribute to central tolerance induction by triggering the unique pro-inflammatory microenvironment in the thymus. In order to complement the existing evidence that has been obtained from mouse models, we performed proteomic analysis on microdissected samples from human thymic medullary areas at different differentiation stages. The analysis confirms that at the post-Aire stages, the mTECs lose their nuclei but maintain machinery required for translation and exocytosis and also upregulate proteins specific to keratinocyte differentiation and cornification. In addition, at the late stages of differentiation, the human mTECs display a distinct pro-inflammatory signature, including upregulation of the potent endogenous TLR4 agonist S100A8/S100A9. Collectively, the study suggests a novel mechanism by which the post-Aire mTECs and Hassall’s corpuscles contribute to the thymic microenvironment with potential cues on the induction of central tolerance.

【 授权许可】

Unknown