Sevilla-Movilla, SilviaFuentes, PatriciaRodríguez-García, YaizaArellano-Sánchez, NohemiKrenn, Peter Wde Val, Soledad IsernMontero-Herradón, SaraGarcía-Ceca, JavierBurdiel-Herencia, ValeriaGardeta, Sofía RAguilera-Montilla, NoemíBarrio-Alonso, CeliaCrainiciuc, GeorgianaBouvard, DanielGarcía-Pardo, AngelesZapata, Agustin GHidalgo, AndresFässler, ReinhardCarrasco, Yolanda RToribio, Maria LTeixidó, Joaquin2023-04-032023-04-032022-08Eur J Immunol. 2022 Aug;52(8):1228-1242http://hdl.handle.net/20.500.12105/15732ICAP-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.engVoRhttp://creativecommons.org/licenses/by/4.0/Adaptor Proteins, Signal TransducingB-LymphocytesCD8-Positive T-LymphocytesLymphocyte ActivationThymocytesAnimalsCell DifferentiationIntegrin beta1MiceMice, KnockoutSpleenThymus GlandICAP-1 loss impairs CD8+ thymocyte development and leads to reduced marginal zone B cells in mice.Atribución 4.0 Internacional35491946528122810.1002/eji.2021495601521-4141European journal of immunologyopen access