Immunodeficiency: primary or acquired
CHU Sainte-Justine Research Center, Montreal, QC, Canada; Department of Biochemistry and Molecular Medicine, University of Montreal; Department of Obstetrics & Gynecology, University of Montreal
Patients with GM-CSF receptor deficiency and patients with anti-GM-CSF autoantibodies commonly suffer from alveolar proteinosis. This rare disorder is also observed in GATA-2 haploinsufficiency. We therefore hypothesized a link between GATA-2 activity and GM-CSF signaling. Confirming our hypothesis, we observed that GATA-2 transcription was increased in response to GM-CSF treatment in human peripheral blood mononuclear cells. By luciferase reporter assay we observed that GM-CSF as well as IL3 pathway activation were able to increase the transcriptional activity of GATA-2. Treatment with specific inhibitors revealed that the signal transduction was mediated by Akt and STAT5. An increase in GATA-2 transcriptional activity was also induced by a constitutively active form of STAT5 in absence of exogenous stimulation. To our knowledge, this is the first demonstration of the link between GATA-2 activity and GM-CSF/IL3/IL5 common beta chain signalling pathway in human immune cells. In addition, our observations likely explain the alveolar proteinosis observed in GATA-2 haploinsufficiency as well as its pleiotropic phenotype.