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

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Sevilla Movilla, Silvia and Fuentes, Patricia and Rodríguez García, Yaiza and Arellano Sánchez, Nohemi and Krenn, Peter W. and Isern de Val, M. Soledad and Montero Herradón, Sara and Garcia-Ceca Hernández, Javier and Burdiel Herencia, Valeria and Gardeta, Sofía R. and Aguilera Montilla, Noemí and Barrio Alonso, Celia and Crainiciuc, Georgiana and Bouvard, Daniel and García-Pardo, Angeles and Zapata González, Agustín and Hidalgo, Andrés and Fässler, Reinhard and Carrasco, Yolanda R. and Toribio, Maria L. and Teixidó, Joaquín (2022) ICAP-1 loss impairs CD8+ thymocyte development and leads to reduced marginal zone B cells in mice. European Journal of Immunology, 52 (8). pp. 1228-1242. ISSN 0014-2980; Electronic: 1521-4141

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Official URL: https://doi.org/10.1002/eji.202149560



Abstract

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.


Item Type:Article
Uncontrolled Keywords:B- cell maturation; Cell adhesion; ICAP-1, Integrins; Thymocyte development
Subjects:Medical sciences > Medicine > Immunology
Medical sciences > Biology > Cytology
ID Code:74676
Deposited On:22 Sep 2022 08:16
Last Modified:22 Sep 2022 10:38

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