Transposable elements regulate thymus development and function

• DOI: 10.7554/elife.91037.3
• Publication Date: 2024-04-18T16:30:40Z
• Authors: Jean-David Larouche; Céline M Laumont; Assya Trofimov; Krystel Vincent; Leslie Hesnard; Sylvie Brochu; Caroline Côté; Juliette F Humeau; Éric Bonneil; Joel Lanoix; Chantal Durette; Patrick Gendron; Jean-Philippe Lav...; Ellen R Richie; Sébastien Lemieux; Pierre Thibault; Claude Perreault
• Keywords: Thymocyte

Transposable elements (TEs) are repetitive sequences representing ~45% of the human and mouse genomes highly expressed by medullary thymic epithelial cells (mTECs). In this study, we investigated role TEs on T-cell development in thymus. We performed multiomic analyses to elucidate their development. report that TE expression thymus is high shows extensive age- cell lineage-related variations. correlates with multiple transcription factors all types Two express particularly broad repertoires: mTECs plasmacytoid dendritic (pDCs). mTECs, transcriptomic data suggest interact essential for mTEC function (e.g., PAX1 REL), immunopeptidomic showed generate MHC-I-associated peptides implicated thymocyte education. Notably, AIRE, FEZF2, CHD4 regulate small yet non-redundant sets murine mTECs. Human pDCs homogenously large numbers likely form dsRNA, which can activate innate immune receptors, potentially explaining why constitutively secrete IFN ɑ/β. This study highlights diversity interactions between adaptive system. genetic parasites, two most affected (mTEcs pDCs) establishing central tolerance. Therefore, propose orchestrating critical prevent autoimmunity vertebrates.