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, de Val, Soledad Isern, Montero-Herradón, Sara, García-Ceca, Javier, Burdiel-Herencia, Valeria, Gardeta, Sofía R, Aguilera-Montilla, Noemí, Barrio-Alonso, Celia, Crainiciuc, Georgiana, Bouvard, Daniel, García-Pardo, Angeles, Zapata, Agustin G, Hidalgo, Andres, Fässler, Reinhard, Carrasco, Yolanda R, Toribio, Maria L, Teixidó, Joaquin
Tipo de recurso: artículo
Fecha de publicación:2022
País:España
Institución:Instituto de Salud Carlos III (ISCIII)
Repositorio:Repisalud
Idioma:inglés
OAI Identifier:oai:repisalud.isciii.es:20.500.12105/15732
Acceso en línea:http://hdl.handle.net/20.500.12105/15732
Access Level:acceso abierto
Palabra clave:Adaptor Proteins, Signal Transducing
B-Lymphocytes
CD8-Positive T-Lymphocytes
Lymphocyte Activation
Thymocytes
Animals
Cell Differentiation
Integrin beta1
Mice
Mice, Knockout
Spleen
Thymus Gland
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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