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MST1 mutations in autosomal recessive primary immunodeficiency characterized by defective naive T-cell survival


Nehme, Nadine T; Schmid, Jana Pachlopnik; Debeurme, Franck; André-Schmutz, Isabelle; Lim, Annick; Nitschke, Patrick; Rieux-Laucat, Frédéric; Lutz, Patrick; Picard, Capucine; Mahlaoui, Nizar; Fischer, Alain; de Saint Basile, Geneviève (2012). MST1 mutations in autosomal recessive primary immunodeficiency characterized by defective naive T-cell survival. Blood, 119(15):3458-3468.

Abstract

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.

Abstract

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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Additional indexing

Item Type:Journal Article, refereed, original work
Communities & Collections:04 Faculty of Medicine > University Children's Hospital Zurich > Medical Clinic
Dewey Decimal Classification:610 Medicine & health
Language:English
Date:2012
Deposited On:01 Mar 2013 13:23
Last Modified:04 Aug 2017 18:50
Publisher:American Society of Hematology
ISSN:0006-4971
Additional Information:This research was originally published in Blood. MST1 mutations in autosomal recessive primary immunodeficiency characterized by defective naive T-cell survival. Copyright by the American Society of Hematology
Free access at:PubMed ID. An embargo period may apply.
Publisher DOI:https://doi.org/10.1182/blood-2011-09-378364
PubMed ID:22174160

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