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Altered thymocyte development observed in EphA4-deficient mice courses with changes in both thymic epithelial and extracellular matrix organization



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García Ceca Hernández, Javier and Montero Herradón, Sara and González, Ana and Plaza, Rosa and Zapata González, Agustín (2022) Altered thymocyte development observed in EphA4-deficient mice courses with changes in both thymic epithelial and extracellular matrix organization. Cellular and Molecular Life Sciences, 79 (11). pp. 1-16. ISSN 1420-682X

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Official URL: https://doi.org/10.1007/s00018-022-04610-w


Eph receptors and their ligands, Ephrins, are involved in the thymocyte-thymic epithelial cell (TEC) interactions, key for the functional maturation of both thymocytes and thymic epithelium. Several years ago, we reported that the lack of EphA4, a Eph of the subfamily A, coursed with reduced proportions of double positive (DP) thymocytes apparently due to an altered thymic epithelial stroma [Munoz et al. in J Immunol 177:804–813, 2006]. In the present study, we reevaluate the lymphoid, epithelial, and extracellular matrix (ECM) phenotype of EphA4−/− mice grouped into three categories with respect to their proportions of DP thymocytes. Our results demonstrate a profound hypocellularity, specifc alterations of T cell diferentiation that afected not only DP thymocytes, but also double negative and single positive T cell subsets, as well as the proportions of positively and negatively selected thymocytes. In correlation, thymic histological organization changed markedly, especially in the cortex, as well as the proportions of both Ly51+UEA-1− cortical TECs and Ly51−UEA-1+ medullary TECs. The alterations observed in the expression of ECM components (Fibronectin, Laminin, Collagen IV), integrin receptors (VLA-4, VLA-6), chemokines (CXCL12, CCL25, CCL21) and their receptors (CXCR4, CCR7, CCR9) and in vitro transwell assays on the capacity of migration of WT and mutant thymocytes suggest that the lack of EphA4 alters T-cell diferentiation by presumably afecting cell adhesion between TECs and T-TEC interactions rather than by thymocyte migration.

Item Type:Article
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CRUE-CSIC (Acuerdos Transformativos 2022)

Uncontrolled Keywords:Thymus; Eph tyrosine kinase receptors; Thymic microenvironments; Cell migration
Subjects:Medical sciences > Medicine > Immunology
Medical sciences > Biology > Cytology
ID Code:75388
Deposited On:07 Nov 2022 09:24
Last Modified:07 Nov 2022 12:33

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