RT Journal Article
T1 Peripheral T-cell responses of EphB2- and EphB3-deficient mice in a model of collagen-induced arthritis
A1 Montero Herradón, Sara
A1 García-Ceca Hernández, José Javier
A1 Villarejo-Torres, Marta
A1 Zapata González, Agustín Gregorio
AB Both EphB2- and EphB3-deficient mice exhibit profound histological alterations in the thymic epithelial network but few changes in T-cell differentiation, suggesting that this organization would be sufficient to produce functional T lymphocytes. Also, other antigen-presenting cells involved in immunological education could substitute the thymic epithelium. Accordingly, we found an increased frequency of plasmacytoid dendritic cells but not of conventional dendritic cells, medullary fibroblasts or intrathymic B lymphocytes. In addition, there are no lymphoid infiltrates in the organs of mutant mice nor do they contain circulating autoantibodies. Furthermore, attempts to induce arthritic lesions after chicken type II collagen administration fail totally in EphB2-deficient mice whereas all WT and half of the immunized EphB3¯/¯ mice develop a typical collagen-induced arthritis. Our results point out that Th17 cells, IL4-producing Th2 cells and regulatory T cells are key for the induction of disease, but mutant mice appear to have deficits in T cell activation or cell migration properties. EphB2-/- T cells show reduced in vitro proliferative responses to anti-CD3/anti-CD28 antibodies, produce low levels of anti-type II collagen antibodies, and exhibit low proportions of T follicular helper cells. On the contrary, EphB3-/- lymph node cells respond accurately to the different immune stimuli although in lower levels than WT cells but show a significantly reduced migration in in vitro transwell assays, suggesting that no sufficient type II collagen-dependent activated lymphoid cells reached the joints, resulting in reduced arthritic lesions.
PB Springer Nature
SN 1420-682X
YR 2024
FD 2024-04-01
LK https://hdl.handle.net/20.500.14352/118931
UL https://hdl.handle.net/20.500.14352/118931
LA eng
NO Montero-Herradón, S., García-Ceca, J., Villarejo-Torres, M., & Zapata, A. G. (2024). Peripheral T-cell responses of EphB2- and EphB3-deficient mice in a model of collagen-induced arthritis. Cellular and Molecular Life Sciences, 81, 159. https://doi.org/10.1007/s00018-024-05197-0
NO Open Access funding provided thanks to the CRUE-CSIC agreement with Springer Nature. This research has been funded by the Spanish Ministry of Science, Innovation and Universities (RTI2018-093938-B-I00) and “Instituto de Salud Carlos III (ISCIII)” through the project RD21/0017/0010, Red Española de Terapias Avanzadas (TERAV, ISCIII), co-funded by the European Union Program “NextGenerationEU” and the “Recovery, Transformation and Resilience Plan”.ContributionsSMH, JGC and AGZ contributed to the study conception and design. Material preparation and data collection were performed by SMH, JGC and MVT. All data were discussed by SMH, JGC and AGZ, the first draft of the manuscript was written by AGZ, and all authors read and approved the final manuscript.
NO Ministerio de Ciencia e Innovación (España)
NO Instituto de Salud Carlos III (ISCIII)
NO Red Española de Terapias Avanzadas
NO Unión Europea
DS Docta Complutense
RD 10 abr 2025