ICAP-1 loss impairs CD8(+) thymocyte development and leads to reduced marginal zone B cells in mice

Sevilla-Movilla, Silvia; Fuentes, Patricia; Rodriguez-Garcia, Yaiza; Arellano-Sanchez, Nohemi; Krenn, Peter W.; Isern de Val, Soledad; Montero-Herradon, Sara; Garcia-Ceca, Javier; Burdiel-Herencia, Valeria; Gardeta, Sofia R.; Aguilera-Montilla, Noemi; Barrio-Alonso, Celia; Crainiciuc, Georgiana; Bouvard, Daniel; Garcia-Pardo, Angeles; Zapata, Agustin G.; Hidalgo, Andres; Fassler, Reinhard; Carrasco, Yolanda R.; Toribio, Maria L. und Teixido, Joaquin (2022): ICAP-1 loss impairs CD8(+) thymocyte development and leads to reduced marginal zone B cells in mice. In: European Journal of Immunology, Bd. 52, Nr. 8: S. 1228-1242

Abstract

ICAP-1 regulates beta 1-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 alpha 4 beta 1-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 alpha 4 beta 1-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.

• Dokumententyp: Zeitschriftenartikel
• Fakultät: Medizin
• Themengebiete: 600 Technik, Medizin, angewandte Wissenschaften > 610 Medizin und Gesundheit
• ISSN: 0014-2980
• Sprache: Englisch