IRIC - Institute for Research in Immunology and Cancer

Published on September 4, 2024

A recent study by the team of Claude Perreault, Director of IRIC’s Immunobiology Research Unit, proposes three potential functions for “parasite” DNA sequences in the development of T lymphocytes. Led by doctoral student Jean-David Larouche, the work is published in the journal eLife.

Strong presence in cells required for the establishment of self-tolerance

T lymphocytes are immune cells involved in the elimination of infected and cancerous cells. “T” stands for the organ in which they complete their development: the thymus. This is where they learn to tolerate the body’s normal cells (i.e. the self) and detect invaders such as infectious agents or cancer cells (the non-self).

Interestingly, DNA fragments called transposable elements are expressed at higher levels in certain thymus cells than in the rest of the body. Referred to as genetic parasites, transposable elements are remnants of viral infections that account for around 45% of the human genome. The fact that their activity is high in the thymus raises an important question: are transposable elements involved in T-cell development?

To answer this question, the Perreault laboratory group carried out multi-omics analyses – a set of techniques enabling the analysis of several thousand indicators simultaneously and providing an overall perspective – in human and murine thymus cells. The data obtained reveal that the expression of transposable elements in the human thymus varies between cell types and during development. Two cell types express transposable elements particularly strongly: medulla thymus epithelial cells (mTECs) and plasmacytoid dendritic cells (pDCs). These two cell populations are essential for the establishment of self-tolerance in T lymphocytes.

Multiple functions for the immune system?

The team identified three potential functions for transposable elements in the thymus. First, by binding numerous transcription factors, they contribute to various gene regulatory networks. Moreover, by stimulating the secretion of certain molecules, they induce a microenvironment that promotes the development of T lymphocytes. Finally, by presenting certain molecular fragments at their surface, they contribute to the education of T lymphocytes. Transposable elements could therefore play several roles in the development and function of the immune system.

These results suggest that the expression of transposable elements in thymus cells is critical for preventing autoimmune reactions in vertebrates. With this new knowledge, the development of effective and safe immunotherapies targeting transposable elements, highly expressed in tumors, could be facilitated.

Cited study

Larouche J-D, Laumont, CM, Trofimov A, Vincent K, Hesnard L, Brochu S, Côté C, Humeau JF, Bonneil É, Lanoix K, Durette C, Gendron P, Laverdure J-P, Richie ER, Lemieux S, Thibault P, Perreault C (2024) Transposable elements regulate thymus development and function, eLife 12:RP91037. https://doi.org/10.7554/eLife.91037.3