Journal
EUROPEAN JOURNAL OF IMMUNOLOGY
Volume 52, Issue 8, Pages 1228-1242Publisher
WILEY
DOI: 10.1002/eji.202149560
Keywords
B- cell maturation; cell adhesion; ICAP-1; integrins; thymocyte development
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Funding
- Ministerio de Ciencia e Innovacion (MICINN) [SAF201785146-R, PID2020-116291RB-I00, PID2019-105623RB-I00, BFU2013-48828-P, RTI2018-095497-B-I00, RTI2018-093938-B-I100]
- ERC
- Instituto de Salud Carlos III [RD16/0011/0002]
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ICAP-1 plays an important role in the development of SP CD8(+) thymocytes and the control of marginal zone B-cell numbers.
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.
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