Medullary epithelium-free areas in the rat thymus are specialized niches enriched for mature thymocytes and distinct stromal subsets
Year: 2026
Type: article
Abstract: The thymic medulla provides the microenvironment for negative selection, late thymocyte maturation, and thymocyte egress, and is generally characterized by widespread distribution of medullary thymic epithelial cells (mTECs). In contrast, the rat thymic medulla contains medullary epithelium-free areas (mEFAs), but the cellular composition and functional significance of these regions remain unclear. Here, to address these questions, we combined spatial transcriptomic data with thymocyte and stromal scRNA-seq reference datasets using robust cell-type decomposition (RCTD) to characterize mEFAs. These analyses revealed that more mature phenotypes within the CD4SP, CD8SP, and regulatory T-cell lineages were preferentially localized in mEFAs, whereas immature SP subsets were enriched in medullary epithelium-containing areas. The newly identified rat thymic mesenchymal cell subsets TMC3 and TMC4 were also enriched in mEFAs. These subsets were broadly similar to mouse medullary fibroblasts but displayed distinct predicted interactions with SP thymocytes, including costimulatory molecule–receptor, chemokine–receptor, and ECM–integrin axes. In addition, venous endothelial cells (vECs) expressing portal endothelial cell markers were enriched in mEFAs. Spns2 , which encodes a transporter that releases S1P from cells into the extracellular space, was preferentially expressed in both TMC4 and vEC subsets, suggesting that these cells may contribute to the formation of a local S1P gradient within mEFAs. These findings suggest that mEFAs may be specialized medullary niches associated with stromal organization, the localization of mature thymocytes, and thymic egress.
Source: Frontiers in Immunology
Authors: Yasushi Sawanobori, Tadayuki Ogawa
Institution: Dokkyo Medical University
Language: English
Topic: T-cell and B-cell Immunology
Subfield: Immunology
Field: Immunology and Microbiology
Domain: Life Sciences
Open Access status: gold
Estimated APC paid: $3,801
OpenAlex ID: W7221805017