A Czech scientist has contributed to understanding the function of the thymus – the training center of the immune system. T lymphocytes, key defensive cells, learn in the thymus not to mistake the body’s own tissues for foreign enemies. A new study by Matouš Vobořil, published in the prestigious Journal of Experimental Medicine, reveals that a broad spectrum of dendritic cells and macrophages also participate in this “education.” The discovery offers crucial insights that could help prevent autoimmune diseases and open new directions for modern immunotherapy.
A comprehensive map of the thymus “faculty”
The thymus acts as a vital “training academy” for our immune system. It is where T lymphocytes – cells responsible for fighting infections and tumors – mature. To protect us effectively without attacking our own tissues, they must undergo rigorous schooling known as central tolerance.
Textbooks in immunology have long described thymic epithelial cells as the main “teachers” of T lymphocytes. However, the new study by Matouš Vobořil, published in The Journal of Experimental Medicine, demonstrates that the teaching process also involves a diverse range of myeloid-lineage cells – including different types of dendritic cells and macrophages – each with specific roles in preventing autoimmunity. The result of years of research is a detailed “faculty roster” of cellular instructors that ensure T cells recognize pathogens while leaving the body’s own tissues unharmed.
The work combines cutting-edge techniques such as single-cell transcriptomics, genetically modified mouse models, and multicolor flow cytometry, providing an exceptionally detailed picture of cellular cooperation within the thymus. The study’s significance is underscored by this year’s Nobel Prize in Physiology or Medicine, awarded for the discovery of regulatory T cells – the very cells that actively suppress autoimmune diseases.
“We have shown that the thymic teaching staff is much more complex than we thought. One type of cell isn’t enough – it takes a whole network of educators working together to shape the immune system,” explains the study’s first author, Matouš Vobořil.
Understanding central tolerance – and beyond
The discovery represents a key contribution to understanding the mechanisms of central tolerance, which protect humans from autoimmune diseases such as multiple sclerosis, type 1 diabetes, and rheumatoid arthritis. In the future, these insights could inspire novel therapeutic or immunomodulatory approaches.
The study shows that central tolerance in the thymus is not maintained solely by epithelial cells or previously known dendritic cell types. Instead, it relies on a complex “faculty” of myeloid-lineage cells – various dendritic cells, macrophages, and even B cells – each with specialized tasks, from antigen presentation to removal of autoreactive T cells.
Main “cellular teachers” in the thymus and their functions
(Cell types newly described or refined in this publication are highlighted below.)
- Thymic epithelial cells (TEC)
- Cortical TEC (cTEC): Mediate positive selection – teaching T cells to recognize self-MHC molecules.
- Medullary TEC (mTEC): Present a wide array of tissue-specific antigens via the transcription factor AIRE, ensuring negative selection of autoreactive T cells.
- Dendritic cells (DC)
- Conventional DC1 (cDC1, XCR1⁺): Present antigens and promote the selection of regulatory T cells.
- Conventional DC2 (cDC2, SIRPα⁺): Interact with other cell types and mediate elimination of autoreactive T cells.
- Migratory (transit) DC: Bring antigens from peripheral tissues during inflammation, providing rapid “remedial lessons” to prevent self-reactivity.
- Plasmacytoid DC (pDC): Transport peripheral antigens to the thymus and help maintain tolerance to environmental antigens.
- Macrophages
- Phagocytose apoptotic T cells that failed selection, preventing release of autoreactive signals.
- May also present antigens and contribute to negative selection.
- Thymic B cells
- Produce and present self-antigens, supporting both the elimination of autoreactive T cells and the selection of regulatory T lymphocytes.
Reference:
Vobořil, M., Sulczewski, F. B., Martinez, R. J., Ashby, K. M., Valerio, M. M., Idoyaga, J., & Hogquist, K. A. (2026). Thymic myeloid cells are heterogeneous and include a novel population of transitional dendritic cells. Journal of Experimental Medicine, 223(1), e20250733. https://doi.org/10.1084/jem.20250733
About the author
Matouš Vobořil, Ph.D. studied biology and immunology at the Faculty of Science, Charles University, where he also earned his doctorate. He conducted most of his PhD research at the Institute of Molecular Genetics of the Czech Academy of Sciences in the laboratory of Dominik Filipp. His dissertation received the Czech Head Award in the “Doctorandus” category.
He completed his postdoctoral training in the laboratory of Kristin Hogquist at the University of Minnesota (USA) and later established his own research group at Charles University’s Faculty of Science thanks to the prestigious GAČR Junior Star grant. His work focuses on T cell development, autoimmunity mechanisms, and antigen-presenting cell function.
The majority of the experimental work was conducted at the Center for Immunology, University of Minnesota Medical School, Minneapolis, USA, in the laboratory of Prof. Kristin Hogquist, with valuable assistance from current and former laboratory members. This study is also the result of a fruitful collaboration with the laboratory of Dr. Juliana Idoyaga at the University of California, San Diego.
About the journal
Founded in 1896, the Journal of Experimental Medicine is one of the world’s most prestigious journals in immunology and biomedical research, ranking in the top decile of journals in its field.