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Here, we used ICAP\u20101\u2010null mice to study ICAP\u20101 potential involvement during immune cell development and function. Integrin \u03b14\u03b21\u2010dependent adhesion was comparable between ICAP\u20101\u2010null and control thymocytes, but lack of ICAP\u20101 caused a defective single\u2010positive (SP) CD8<jats:sup>+<\/jats:sup> cell generation, thus, unveiling an ICAP\u20101 involvement in SP thymocyte development. ICAP\u20101 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\u20101 and reduced levels in SP CD8<jats:sup>+<\/jats:sup> thymocytes of Runx3, a transcription factor required for CD8<jats:sup>+<\/jats:sup> thymocyte generation. In the spleen, ICAP\u20101 was found evenly distributed between cytoplasm and nuclear fractions, and ICAP\u20101<jats:sup>\u2013\/\u2013<\/jats:sup> spleen T and B cells displayed upregulation of \u03b14\u03b21\u2010mediated adhesion, indicating that ICAP\u20101 negatively controls their attachment. Furthermore, CD3<jats:sup>+<\/jats:sup>\u2010 and CD19<jats:sup>+<\/jats:sup>\u2010selected spleen cells from ICAP\u20101\u2010null mice showed reduced proliferation in response to T\u2010 and B\u2010cell stimuli, respectively. Finally, loss of ICAP\u20101 caused a remarkable decrease in marginal zone B\u2010 cell frequencies and a moderate increase in follicular B cells. Together, these data unravel an ICAP\u20101 involvement in the generation of SP CD8<jats:sup>+<\/jats:sup> thymocytes and in the control of marginal zone B\u2010cell numbers.<\/jats:p>","DOI":"10.1002\/eji.202149560","type":"journal-article","created":{"date-parts":[[2022,5,2]],"date-time":"2022-05-02T09:34:36Z","timestamp":1651484076000},"page":"1228-1242","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["ICAP\u20101 loss impairs CD8<sup>+<\/sup> thymocyte development and leads to reduced marginal zone B cells in mice"],"prefix":"10.1002","volume":"52","author":[{"given":"Silvia","family":"Sevilla\u2010Movilla","sequence":"first","affiliation":[{"name":"Department of Molecular Biomedicine Centro de Investigaciones Biol\u00f3gicas Margarita Salas (CSIC)  Madrid 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