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

Autor: Sevilla-Movilla S; Department of Molecular Biomedicine, Centro de Investigaciones Biológicas Margarita Salas (CSIC), Madrid, Spain., Fuentes P; Development and Function of the Immune System Unit, Centro de Biología Molecular Severo Ochoa, CSIC, Universidad Autónoma de Madrid, Madrid, Spain., Rodríguez-García Y; Department of Molecular Biomedicine, Centro de Investigaciones Biológicas Margarita Salas (CSIC), Madrid, Spain., Arellano-Sánchez N; Department of Molecular Biomedicine, Centro de Investigaciones Biológicas Margarita Salas (CSIC), Madrid, Spain., Krenn PW; Department of Molecular Medicine, Max Planck Institute of Biochemistry, Martinsried, Germany.; Department of Biosciences and Medical Biology, Cancer Cluster Salzburg, Paris-Lodron University of Salzburg, Salzburg, Austria., de Val SI; Department of Molecular Biomedicine, Centro de Investigaciones Biológicas Margarita Salas (CSIC), Madrid, Spain., Montero-Herradón S; Department of Cell Biology, Faculty of Biology, Complutense University of Madrid, Madrid.; Spain and Health Research Institute, Hospital 12 de Octubre (imas12), Madrid, Spain., García-Ceca J; Department of Cell Biology, Faculty of Biology, Complutense University of Madrid, Madrid.; Spain and Health Research Institute, Hospital 12 de Octubre (imas12), Madrid, Spain., Burdiel-Herencia V; Department of Molecular Biomedicine, Centro de Investigaciones Biológicas Margarita Salas (CSIC), Madrid, Spain., Gardeta SR; Department on Immunology and Oncology, Centro Nacional de Biotecnología (CNB)-CSIC, Madrid, Spain., Aguilera-Montilla N; Department of Molecular Biomedicine, Centro de Investigaciones Biológicas Margarita Salas (CSIC), Madrid, Spain., Barrio-Alonso C; Department of Molecular Biomedicine, Centro de Investigaciones Biológicas Margarita Salas (CSIC), Madrid, Spain.; Hospital General Universitario Gregorio Marañón, Madrid, Spain., Crainiciuc G; Hospital General Universitario Gregorio Marañón, Madrid, Spain.; Area of Developmental and Cell Biology, Centro Nacional de Investigaciones Cardiovasculares Carlos III (CNIC), Madrid, Spain., Bouvard D; Centre de Recherche en Biologie Cellulaire de Montpellier, Montpellier, France., García-Pardo A; Department of Molecular Biomedicine, Centro de Investigaciones Biológicas Margarita Salas (CSIC), Madrid, Spain., Zapata AG; Department of Cell Biology, Faculty of Biology, Complutense University of Madrid, Madrid.; Spain and Health Research Institute, Hospital 12 de Octubre (imas12), Madrid, Spain., Hidalgo A; Institute for Cardiovascular Prevention, Ludwig-Maximilians University, Munich, 80336, Germany.; Area of Developmental and Cell Biology, Centro Nacional de Investigaciones Cardiovasculares Carlos III (CNIC), Madrid, Spain., Fässler R; Department of Molecular Medicine, Max Planck Institute of Biochemistry, Martinsried, Germany., Carrasco YR; Department on Immunology and Oncology, Centro Nacional de Biotecnología (CNB)-CSIC, Madrid, Spain., Toribio ML; Development and Function of the Immune System Unit, Centro de Biología Molecular Severo Ochoa, CSIC, Universidad Autónoma de Madrid, Madrid, Spain., Teixidó J; Department of Molecular Biomedicine, Centro de Investigaciones Biológicas Margarita Salas (CSIC), Madrid, Spain.
Jazyk: angličtina
Zdroj: European journal of immunology [Eur J Immunol] 2022 Aug; Vol. 52 (8), pp. 1228-1242. Date of Electronic Publication: 2022 May 13.
DOI: 10.1002/eji.202149560
Abstrakt: 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.
(© 2022 The Authors. European Journal of Immunology published by Wiley-VCH GmbH.)
Databáze: MEDLINE
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