The alarmin IL33 marks a thymocyte dependent shift in the makeup of cortical thymic epithelial cells
- 1Department of Immunology and Immunotherapy, School of Infection, Inflammation and Immunology, College of Medicine and Health, University of Birmingham
Abstract
Functional competence in the adaptive immune system requires the generation of αβT-cells in the thymus, where thymic epithelial cells (TEC) drive thymocyte development. Roles for cortical thymic epithelial cells (cTEC) include the generation of CD4 ⁺ CD8 ⁺ thymocytes, and positive selection of cells capable of self-peptide/MHC recognition. Recently, we showed that, in the adult thymus, cTEC consist of two distinct subsets, Foxn1 ⁺ typical and Foxn1 ⁻ atypical cells. While typical cTEC regulate thymopoiesis through their expression of Psmb11 , Cxcl12 and Dll4 , the developmental requirements and properties of atypical cTEC remain undefined. Here, we show atypical cTEC downregulate the expression of multiple genes controlling antigen processing and presentation for positive selection including Psmb11 , Cd83 , Prss16 , and Ctsl . In addition, we show atypical cTEC acquire a distinct gene profile including the chemokines Ccl9 and Ccl11 together with the alarmin Il33 that plays an essential role in thymic repair following injury. Using precursor-product analysis and Cxcl12/Il33 dual reporter mice, we show Il33 -expressing atypical cTEC can be generated from typical cTEC that lack Il33 expression, a process which depends upon progression beyond the pre-TCR-mediated checkpoint. Together, these data define thymocyte-dependent changes in the adult cTEC compartment and suggest atypical cTEC may acquire functional properties that are distinct from their typical cTEC counterparts, including the possibility of acting as an additional source of IL33 in pathways of thymic regeneration.
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BibTeX
@article{white2026alarmin,
title = {{The alarmin IL33 marks a thymocyte dependent shift in the makeup of cortical thymic epithelial cells}},
author = {Andrea J. White and Sonia M. Parnell and Fabrina M. Gaspal and Andrea Bacon and Nahim A. Nurjahan and William E. Jenkinson and Graham Anderson and Kieran D. James},
journal = {Frontiers in Immunology},
year = {2026},
month = oct,
doi = {10.3389/fimmu.2026.1974594},
url = {https://www.frontiersin.org/articles/10.3389/fimmu.2026.1974594/full},
note = {CC BY 4.0},
}
RIS
TY - JOUR
TI - The alarmin IL33 marks a thymocyte dependent shift in the makeup of cortical thymic epithelial cells
AU - Andrea J. White
AU - Sonia M. Parnell
AU - Fabrina M. Gaspal
AU - Andrea Bacon
AU - Nahim A. Nurjahan
AU - William E. Jenkinson
AU - Graham Anderson
AU - Kieran D. James
PY - 2026
DA - 2026/10/27
JO - Frontiers in Immunology
DO - 10.3389/fimmu.2026.1974594
UR - https://www.frontiersin.org/articles/10.3389/fimmu.2026.1974594/full
AB - Functional competence in the adaptive immune system requires the generation of αβT-cells in the thymus, where thymic epithelial cells (TEC) drive thymocyte development. Roles for cortical thymic epithelial cells (cTEC) include the generation of CD4 ⁺ CD8 ⁺ thymocytes, and positive selection of cells capable of self-peptide/MHC recognition. Recently, we showed that, in the adult thymus, cTEC consist of two distinct subsets, Foxn1 ⁺ typical and Foxn1 ⁻ atypical cells. While typical cTEC regulate thymopoiesis through their expression of Psmb11 , Cxcl12 and Dll4 , the developmental requirements and properties of atypical cTEC remain undefined. Here, we show atypical cTEC downregulate the expression of multiple genes controlling antigen processing and presentation for positive selection including Psmb11 , Cd83 , Prss16 , and Ctsl . In addition, we show atypical cTEC acquire a distinct gene profile including the chemokines Ccl9 and Ccl11 together with the alarmin Il33 that plays an essential role in thymic repair following injury. Using precursor-product analysis and Cxcl12/Il33 dual reporter mice, we show Il33 -expressing atypical cTEC can be generated from typical cTEC that lack Il33 expression, a process which depends upon progression beyond the pre-TCR-mediated checkpoint. Together, these data define thymocyte-dependent changes in the adult cTEC compartment and suggest atypical cTEC may acquire functional properties that are distinct from their typical cTEC counterparts, including the possibility of acting as an additional source of IL33 in pathways of thymic regeneration.
SN - 1664-3224
ER -