Transposable elements regulate thymus development and function

• DOI: 10.7554/elife.91037.2
• Publication Date: 2024-04-05T12:25:17Z
• Authors: Jean-David Larouche; Céline M. Laumont; Assya Trofimov; Krystel Vincent; Leslie Hesnard; Sylvie Brochu; Caroline Côté; Juliette Humeau; Éric Bonneil; Joël Lanoix; Chantal Durette; Patrick Gendron; Jean-Philippe Lav...; Ellen R. Richie; Sébastien Lemieux; Pierre Thibault; Claude Perreault
• Keywords: QH301-705.5; Science; Thymus Gland; Mice; 03 medical and health sciences; thymus; Humans; Animals; Biology (General); central tolerance; 0303 health sciences; Thymocytes; Q; R; AIRE Protein; Genetics and Genomics; Epithelial Cells; Cell Differentiation; 3. Good health; Mice, Inbred C57BL; plasmacytoid dendritic cells; thymic epithelial cells; DNA Transposable Elements; Medicine; transposable elements; Transcription Factors

Transposable elements (TE) are repetitive sequences representing ∼45% of the human and mouse genomes highly expressed by medullary thymic epithelial cells (mTEC). In this study, we investigated role TEs on T-cell development in thymus. We performed multi-omic analyses to elucidate their T cell development. report that TE expression thymus is high shows extensive age- lineage-related variations. correlates with multiple transcription factors all types Two express particularly broad repertoires: mTECs plasmacytoid dendritic (pDC). 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 LJ/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.