The thymus hosts more ‘cellular teachers’ than we thought, study finds

Spread the love
The thymus has more 'cellular teachers' than we thought
scRNA-seq reveals heterogeneity in thymic DCs. (A) scRNA-seq of CD11c+ and CD11b+ FACS-sorted cells from the thymus of 7-wk-old C57BL/6 mice. UMAP plots show the analysis of 11,586 transcriptome events, with dashed lines representing clusters expressing Flt3, Csf1r, and Csf3r. (B) Feature plots showing the normalized expression of Flt3, Csf1r, and Csf3r in the clusters defined in A. (C) UMAP plots show the analysis of 8,514 transcriptome events and identify 16 clusters of thymic myeloid cells. Violin plots show the normalized expression of signature genes in these clusters. (D) Representative flow cytometry gating strategy for pre-gating thymic myeloid cells. (E) Representative gating strategy for identifying thymic neutrophils (Ly6G/SiglecF+Ly6C+CD11c−) and eosinophils (Ly6G/SiglecF+Ly6C−CD11c+). The graph shows the total numbers of neutrophils and eosinophils per thymus in 7-wk-old C57BL/6 mice; n = 3 mice. Data are shown as mean ± SD. Credit: Charles University

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 from the Faculty of Science, Charles University, Prague, published in the 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 Vobořil 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, 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. https://medicalxpress.com/news/2025-10-thymus-hosts-cellular-teachers-thought.html