RT Journal Article T1 ICAP-1 loss impairs CD8+ thymocyte development and leads to reduced marginal zone B cells in mice A1 Sevilla Movilla, Silvia A1 Fuentes, Patricia A1 Rodríguez García, Yaiza A1 Arellano Sánchez, Nohemi A1 Krenn, Peter W. A1 Isern de Val, M. Soledad A1 Montero Herradón, Sara A1 Garcia-Ceca Hernández, Javier A1 Burdiel Herencia, Valeria A1 Gardeta, Sofía R. A1 Aguilera Montilla, Noemí A1 Barrio Alonso, Celia A1 Crainiciuc, Georgiana A1 Bouvard, Daniel A1 García-Pardo, Angeles A1 Zapata González, Agustín A1 Hidalgo, Andrés A1 Fässler, Reinhard A1 Carrasco, Yolanda R. A1 Toribio, Maria L. A1 Teixidó, Joaquín AB 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. PB Wiley SN 0014-2980; Electronic: 1521-4141 YR 2022 FD 2022-05-02 LK https://hdl.handle.net/20.500.14352/72021 UL https://hdl.handle.net/20.500.14352/72021 LA eng NO Ministerio de Ciencia e Innovación (MICINN) NO Instituto de Salud Carlos III (ISCIII) DS Docta Complutense RD 6 abr 2025