Delayed maturation of thymic epithelium in mice with specific deletion of β-catenin gene in FoxN1 positive cells
Autor: | Sara Montero-Herradón, Agustín G. Zapata |
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Rok vydání: | 2021 |
Předmět: |
0301 basic medicine
Histology Cell Inmunología Mice Transgenic Thymus Gland Biology Epithelium Mice Mice Congenic 03 medical and health sciences 0302 clinical medicine medicine Animals Progenitor cell Molecular Biology Wnt signalling beta Catenin Mice Knockout Original Paper Thymocytes Biología celular FOXN1 Forkhead Transcription Factors Cell Biology β-catenin Embryonic stem cell Cell biology Medical Laboratory Technology Thymocyte 030104 developmental biology medicine.anatomical_structure Hypocellularity Catenin Thymic epithelial cells (TECs) CCL25 030215 immunology |
Zdroj: | E-Prints Complutense. Archivo Institucional de la UCM instname Histochemistry and Cell Biology |
ISSN: | 1432-119X 0948-6143 |
Popis: | Wnt signalling pathways have been reported to be involved in thymus development but their precise role in the development of both thymic epithelium (TE) and thymocytes is controversial. Herein, we examined embryonic, postnatal and adult thymi of mice with a specific deletion of β-catenin gene in FoxN1+ thymic epithelial cells (TECs). Together with a high postnatal mouse mortality, the analysis showed severe thymic hypocellularity, largely due an important reduction in numbers of developing thymocytes, and delayed, partially blocked maturation of mutant TECs. Affected TECs included largely cortical (c) TEC subsets, such as immature MTS20+ TECs, Ly51+ cTECs and a remarkable, rare Ly51+MTS20+MHCIIhi cell subpopulation previously reported to contain thymic epithelial progenitor cells (TEPCs) (Ulyanchenko et al., Cell Rep 14:2819–2832, 2016). In addition, altered postnatal organization of mutant thymic medulla failed to organize a unique, central epithelial area. This delayed maturation of TE cell components correlated with low transcript production of some molecules reported to be masters for TEC maturation, such as EphB2, EphB3 and RANK. Changes in the thymic lymphoid component became particularly evident after birth, when molecules expressed by TECs and involved in early T-cell maturation, such as CCL25, CXCL12 and Dll4, exhibited minimal values. This represented a partial blockade of the progression of DN to DP cells and reduced proportions of this last thymocyte subset. At 1 month, in correlation with a significant increase in transcript production, the DP cell percentage increased in correlation with a significant fall in the number of mature TCRαβhi thymocytes and peripheral T lymphocytes. |
Databáze: | OpenAIRE |
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