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

作者：Nehme Nadine T; Schmid Jana Pachlopnik; Debeurme Franck; Andre Schmutz Isabelle; Lim Annick; Nitschke Patrick; Rieux Laucat Frederic; Lutz Patrick; Picard Capucine; Mahlaoui Nizar; Fischer Alain; de Saint Basile Genevieve^*

来源：Blood, 2012, 119(15): 3458-3468.

DOI：10.1182/blood-2011-09-378364

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. (Blood. 2012;119(15):3458-3468)

• 出版日期2012-4-12