RT Journal Article
T1 Altered thymocyte development observed in EphA4-deficient mice courses with changes in both thymic epithelial and extracellular matrix organization
A1 García-Ceca Hernández, José Javier
A1 Montero Herradón, Sara
A1 González, Ana
A1 Plaza, Rosa
A1 Zapata González, Agustín Gregorio
AB 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, specific alterations of T cell differentiation that affected 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 differentiation by presumably affecting cell adhesion between TECs and T-TEC interactions rather than by thymocyte migration.
PB Springer Nature
SN 1420-682X
YR 2022
FD 2022-11-05
LK https://hdl.handle.net/20.500.14352/124039
UL https://hdl.handle.net/20.500.14352/124039
LA eng
NO García-Ceca, J., Montero-Herradón, S., González, A., Plaza, R., & Zapata, A. G. (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). https://doi.org/10.1007/S00018-022-04610-W
NO Open Access funding provided thanks to the CRUE-CSIC agreement with Springer Nature. This research was funded by the Spanish Ministry of Science, Innovation and Universities (RTI2018-093938-B-I00), the Carlos III Health Institute (RD16/0011/0002, Cell Therapy Network, TERCEL; RD21/0017/0010, RICORS TERAV) and the Regional Government of Madrid (S2017/BMD-3692, Avancell).
NO Conferencia de Rectores de las Universidades Españolas
NO Consejo Superior de Investigaciones Científicas (España)
NO Ministerio de Ciencia, Innovación y Universidades ( España)
NO Instituto de Salud Carlos III
NO Comunidad de Madrid
DS Docta Complutense
RD 28 sept 2025