ICAP-1 loss impairs CD8+ thymocyte development and leads to reduced marginal zone B cells in mice
| Autor: | Silvia Sevilla‐Movilla, Patricia Fuentes, Yaiza Rodríguez‐García, Nohemi Arellano‐Sánchez, Peter W. Krenn, Soledad Isern de Val, Sara Montero‐Herradón, Javier García‐Ceca, Valeria Burdiel‐Herencia, Sofía R. Gardeta, Noemí Aguilera‐Montilla, Celia Barrio‐Alonso, Georgiana Crainiciuc, Daniel Bouvard, Angeles García‐Pardo, Agustin G. Zapata, Andrés Hidalgo, Reinhard Fässler, Yolanda R. Carrasco, Maria L. Toribio, Joaquin Teixidó |
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| Přispěvatelé: | Ministerio de Ciencia e Innovación (España), Instituto de Salud Carlos III, Unión Europea. Comisión Europea. European Research Council (ERC), Sevilla-Movilla, Silvia [0000-0002-4651-1813], Fuentes, Patricia [0000-0003-4597-1022], Arellano-Sánchez, Nohemí [0000-0002-9309-6931], Isern de Val, Soledad [0000-0002-1303-706X], Montero-Herradón, Sara [0000-0003-2004-8987], Gardeta, Sofía [0000-0003-1166-4809], Aguilera-Montilla, Noemí [0000-0002-6925-6069], Crainiciuc, Georgiana [0000-0002-0912-7425], García-Pardo, Angeles [0000-0001-5577-2954], Zapata, Agustín G. [0000-0003-0576-2672], Hidalgo, Andrés [0000-0001-5513-555X], Carrasco, Yolanda R. [0000-0003-2148-1926, Toribio, María Luisa [0000-0002-8637-0373], Teixidó, Joaquín [0000-0002-3177-4151], Sevilla-Movilla, Silvia, Fuentes, Patricia, Arellano-Sánchez, Nohemí, Isern de Val, Soledad, Montero-Herradón, Sara, Gardeta, Sofía, Aguilera-Montilla, Noemí, Crainiciuc, Georgiana, García-Pardo, Angeles, Zapata, Agustín G., Hidalgo, Andrés, Carrasco, Yolanda R., Toribio, María Luisa, Teixidó, Joaquín |
| Jazyk: | angličtina |
| Rok vydání: | 2022 |
| Předmět: |
Mice
Knockout ICAP-1 Integrins B-Lymphocytes Thymocytes Biología celular B cell maturation Integrin beta1 Immunology Inmunología Cell adhesion Cell Differentiation Thymus Gland CD8-Positive T-Lymphocytes Lymphocyte Activation Mice Immunology and Allergy Animals Spleen Thymocyte development Adaptor Proteins Signal Transducing |
| Zdroj: | E-Prints Complutense. Archivo Institucional de la UCM instname Digital.CSIC. Repositorio Institucional del CSIC |
| ISSN: | 2017-8514 |
| Popis: | 41 p.-7 fig. 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. This work was supported by grants SAF2017-85146-R and PID2020-116291RB-I00 from the Ministerio de Ciencia e Innovación (MICINN) to J.T, PID2019-105623RB-I00 from MICINN to M.L.T,BFU2013-48828-P from MICINN to Y.R.C., ERC Synergy Grant (2018) to R.F., RTI2018-095497-B-I00 from MICINN to A.H, and RTI2018-093938-B-I100 from MICINN and (RD16/0011/0002, TERCEL) from Instituto de Salud Carlos III to AGZ. |
| Databáze: | OpenAIRE |
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