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MST1 mutations in autosomal recessive primary immunodeficiency characterized by defective naive T-cell survival
Open accessAbstract
The molecular mechanisms that underlie T-cell quiescence are poorly understood. In the present study, we report a primary immunodeficiency phenotype associated with MST1 deficiency and primarily characterized by a progressive loss of naive T cells. The in vivo consequences include recurrent bacterial and viral infections and autoimmune manifestations. MST1-deficient T cells poorly expressed the transcription factor FOXO1, the IL-7 receptor, and BCL2. Conversely, FAS expression and the FAS-mediating apoptotic pathway were up-regulated. These abnormalities suggest that increased cell death of naive and proliferating T cells is the main mechanism underlying this novel immunodeficiency. Our results characterize a new mechanism in primary T-cell immunodeficiencies and highlight a role of the MST1/FOXO1 pathway in controlling the death of human naive T cells.
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Cites
Forkhead transcription factor FOXO3a protects quiescent cells from oxidative stress
Kops, G. J. P. L., Dansen, T. B., Polderman, P. E., Saarloos, I., Wirtz, K. W. A., Coffer, P. J., Huang, T.-T., Bos, J. L., Medema, R. H., & Burgering, B. M. T. (2002) · Nature · doi:10.1038/nature01036 · Cited by 1,580
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Papagno, L., Spina, C. A., Marchant, A., Salio, M., Rufer, N., Little, S., Dong, T., Chesney, G., Waters, A., Easterbrook, P., et al. (2004) · PLoS Biology · doi:10.1371/journal.pbio.0020020 · Cited by 478
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Metadata
- Authors
- Nehme, N. T., Schmid, J. P., Debeurme, F., André-Schmutz, I., Lim, A., Nitschke, P., Rieux-Laucat, F., Lutz, P., Picard, C., Mahlaoui, N., Fischer, A., & de Saint Basile, G.
- Venue
- Blood
- Publisher
- American Society of Hematology
- Published
- 2012-04-12
- Volume
- 119
- Issue
- 15
- Pages
- 3458-3468
- ISSN
- 0006-4971 (ISSN-L)
- 1528-0020
- OpenAlex
- W2072367725
- Cited by
- 283
- References
- 2
- FWCI
- 7.00
- Type
- journal article
- Language
- en
- Open access
- bronze
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Contains information from the Semantic Scholar Academic Graph Datasets, made available under the ODC Attribution License (ODC-BY 1.0).
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