title: MST1 mutations in autosomal recessive primary immunodeficiency characterized by defective naive T-cell survival.
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.
authors.affiliation: Inserm U768, Paris, France.|Université Paris Descartes, Sorbone Paris Cité, Faculté de Médecine, Necker Hospital, Paris, France.
authors.forename: Nadine T
authors.initials: NT
authors.lastname: Nehme
authors.affiliation: Inserm U768, Paris, France.|Université Paris Descartes, Sorbone Paris Cité, Faculté de Médecine, Necker Hospital, Paris, France.
authors.forename: Jana Pachlopnik
authors.initials: JP
authors.lastname: Schmid
authors.affiliation: Inserm U768, Paris, France.|Université Paris Descartes, Sorbone Paris Cité, Faculté de Médecine, Necker Hospital, Paris, France.
authors.forename: Franck
authors.initials: F
authors.lastname: Debeurme
authors.affiliation: Inserm U768, Paris, France.|Université Paris Descartes, Sorbone Paris Cité, Faculté de Médecine, Necker Hospital, Paris, France.
authors.forename: Isabelle
authors.initials: I
authors.lastname: André-Schmutz
authors.affiliation: Inserm U668 and Lymphocyte Development Unit, Institut Pasteur, Paris, France.
authors.forename: Annick
authors.initials: A
authors.lastname: Lim
authors.affiliation: Service de Bioinformatique, Université Paris Descartes, Paris, France.
authors.forename: Patrick
authors.initials: P
authors.lastname: Nitschke
authors.affiliation: Inserm U768, Paris, France.|Université Paris Descartes, Sorbone Paris Cité, Faculté de Médecine, Necker Hospital, Paris, France.
authors.forename: Frédéric
authors.initials: F
authors.lastname: Rieux-Laucat
authors.affiliation: Unité d'Hématologie Pédiatrique, Hôpital de Hautepierre, Strasbourg, France.
authors.forename: Patrick
authors.initials: P
authors.lastname: Lutz
authors.affiliation: Université Paris Descartes, Sorbone Paris Cité, Faculté de Médecine, Necker Hospital, Paris, France.|Centre d'Etudes des Déficits Immunitaires, Assistance Publique-Hôpitaux de Paris (AP-HP) Hôpital Necker, Paris, France.|Inserm U980, Necker Medical Schoool, Paris, France.|AP-HP Hôpital Necker-Enfants Malades, Pediatric Immuno-Hematology Unit and National Referral Center for Primary Immune Deficiencies, Paris, France.
authors.forename: Capucine
authors.initials: C
authors.lastname: Picard
authors.affiliation: Université Paris Descartes, Sorbone Paris Cité, Faculté de Médecine, Necker Hospital, Paris, France.|AP-HP Hôpital Necker-Enfants Malades, Pediatric Immuno-Hematology Unit and National Referral Center for Primary Immune Deficiencies, Paris, France.
authors.forename: Nizar
authors.initials: N
authors.lastname: Mahlaoui
authors.affiliation: Inserm U768, Paris, France.|Université Paris Descartes, Sorbone Paris Cité, Faculté de Médecine, Necker Hospital, Paris, France.|AP-HP Hôpital Necker-Enfants Malades, Pediatric Immuno-Hematology Unit and National Referral Center for Primary Immune Deficiencies, Paris, France.
authors.forename: Alain
authors.initials: A
authors.lastname: Fischer
authors.affiliation: Inserm U768, Paris, France.|Université Paris Descartes, Sorbone Paris Cité, Faculté de Médecine, Necker Hospital, Paris, France.|Centre d'Etudes des Déficits Immunitaires, Assistance Publique-Hôpitaux de Paris (AP-HP) Hôpital Necker, Paris, France.|AP-HP Hôpital Necker-Enfants Malades, Pediatric Immuno-Hematology Unit and National Referral Center for Primary Immune Deficiencies, Paris, France.
authors.forename: Geneviève
authors.initials: G
authors.lastname: de Saint Basile
mesh_terms: D000293:Adolescent; D002470:Cell Survival / Q000235:genetics; D002478:Cells, Cultured; D002648:Child; D002675:Child, Preschool; D005190:Family; D005260:Female; D005808:Genes, Recessive / Q000502:physiology; D006801:Humans; D007153:Immunologic Deficiency Syndromes / Q000097:blood / Q000235:genetics* / Q000276:immunology*; D047908:Intracellular Signaling Peptides and Proteins; D008297:Male; D009154:Mutation / Q000502:physiology; D010375:Pedigree; D017346:Protein Serine-Threonine Kinases / Q000235:genetics*; D013601:T-Lymphocytes / Q000276:immunology / Q000502:physiology*; D000099317:Hippo Kinases
chemical_list: D047908:Intracellular Signaling Peptides and Proteins; D017346:Protein Serine-Threonine Kinases; C095566:STK4 protein, human; D000099317:Hippo Kinases