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

NT Nehme, JP Schmid, F Debeurme… - Blood, The Journal …, 2012 - ashpublications.org
NT Nehme, JP Schmid, F Debeurme, I André-Schmutz, A Lim, P Nitschke, F Rieux-Laucat…
Blood, The Journal of the American Society of Hematology, 2012ashpublications.org
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 …
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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