ICAP-1 loss impairs CD8+ thymocyte development and leads to reduced marginal zone B cells in mice

ICAP-1 regulates β1-integrin activation and cell adhesion. Here, we used ICAP-1-null mice to study ICAP-1 potential involvement during immune cell development and function. Integrin α4β1-dependent adhesion was comparable between ICAP-1-null and control thymocytes, but lack of ICAP-1 caused a defecti...

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Detalles Bibliográficos
Autores: Sevilla Movilla, Silvia, Fuentes, Patricia, Rodríguez García, Yaiza, Arellano Sánchez, Nohemi, Krenn, Peter W., Isern de Val, M. Soledad, Montero Herradón, Sara, Garcia-Ceca Hernández, Javier, Burdiel Herencia, Valeria, Gardeta, Sofía R., Aguilera Montilla, Noemí, Barrio Alonso, Celia, Crainiciuc, Georgiana, Bouvard, Daniel, García-Pardo, Angeles, Zapata González, Agustín, Hidalgo, Andrés, Fässler, Reinhard, Carrasco, Yolanda R., Toribio, Maria L., Teixidó, Joaquín
Tipo de recurso: artículo
Fecha de publicación:2022
País:España
Institución:Universidad Complutense de Madrid (UCM)
Repositorio:Docta Complutense
Idioma:inglés
OAI Identifier:oai:docta.ucm.es:20.500.14352/72021
Acceso en línea:https://hdl.handle.net/20.500.14352/72021
Access Level:acceso abierto
Palabra clave:577.27
611.438
B- cell maturation
Cell adhesion
ICAP-1
Integrins
Thymocyte development
Inmunología
Biología celular (Biología)
2412 Inmunología
2407 Biología Celular
Descripción
Sumario:ICAP-1 regulates β1-integrin activation and cell adhesion. Here, we used ICAP-1-null mice to study ICAP-1 potential involvement during immune cell development and function. Integrin α4β1-dependent adhesion was comparable between ICAP-1-null and control thymocytes, but lack of ICAP-1 caused a defective single-positive (SP) CD8+ cell generation, thus, unveiling an ICAP-1 involvement in SP thymocyte development. ICAP-1 bears a nuclear localization signal and we found it displayed a strong nuclear distribution in thymocytes. Interestingly, there was a direct correlation between the lack of ICAP-1 and reduced levels in SP CD8+ thymocytes of Runx3, a transcription factor required for CD8+ thymocyte generation. In the spleen, ICAP-1 was found evenly distributed between cytoplasm and nuclear fractions, and ICAP-1–/– spleen T and B cells displayed upregulation of α4β1-mediated adhesion, indicating that ICAP-1 negatively controls their attachment. Furthermore, CD3+- and CD19+-selected spleen cells from ICAP-1-null mice showed reduced proliferation in response to T- and B-cell stimuli, respectively. Finally, loss of ICAP-1 caused a remarkable decrease in marginal zone B- cell frequencies and a moderate increase in follicular B cells. Together, these data unravel an ICAP-1 involvement in the generation of SP CD8+ thymocytes and in the control of marginal zone B-cell numbers.

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