The team of Dr. Julie Lessard, principal investigator at the Institute for Research in Immunology and Cancer (IRIC) at the Université de Montréal and professor at the Department of Pathology and Cell Biology of the Faculty of Medicine, published a study in the prestigious scientific journal Nature Genetics. Conducted in collaboration with Dr. Louis Gaboury and Dr. Guy Sauvageau, principal investigators at IRIC, this study describes the discovery of a key mechanism in the production of white blood cells specialized in defending the body against infections.
The Body’s First Respondents
Gene SMARCD2 is essential in the production of neutrophils and eosinophils—specialized cells which defend the host against pathogens (also called the innate immune system). They are highly abundant in the human blood: in a normal individual, they represent around 50–60% of blood cells. Those guards are normally the first cells to arrive at the site of an infection.
The bone marrow of a healthy adult produce more than 100 billion neutrophils every day; a number that can be multiplied by up to ten during acute inflammation.
In the laboratory of Julie Lessard, the team found that suppressing gene SMARCD2 in mice causes a blockage in the production of immune cells in the bone marrow, leading to premature death.
An Immune Disease with Similar Symptoms
This observation recalls a human congenital disorder called “specific granule deficiency” (SGD), which not only causes severe infections due to the lack of neutrophils, but is also often linked to a myelodysplastic syndrome that can develop into leukemia.
Though the first patients affected by this syndrome have been listed in the early 1970s, the molecular basis of this disease of the immune system is yet to be fully understood.
A study completed by the team of Dr. Christoph Klein in Germany, and published in the same issue of the journal, identified mutations in gene SMARCD2 in patients affected by this disease, thus demonstrating that the function of this gene is maintained in humans.
“Our studies led to the discovery of a critical regulator of the innate immune response and provide a better understanding of the molecular defects responsible for a disease of the immune system,” explains Pierre Priam, Ph.D. candidate in the laboratory of Julie Lessard, and first author of this paper.
Priam P., Krasteva V., Rousseau P., D’Angelo G., Gaboury L., Sauvageau G. and Lessard JA. Smarcd2 Subunit of SWI/SNF Chromatin-remodeling Complexes Mediates Granulopoiesis through a CEBPe-Dependent Mechanism. Nature Genetics. Advance Online Publication April 3, 2017. DOI: 10.1038/ng.3812. View abstract and full article
About the Institute for Research in Immunology and Cancer (IRIC)
An ultra-modern research hub and training centre located in the heart of the Université de Montreal, IRIC was created in 2003 to shed light on the mechanisms of cancer and discover new, more effective therapies to counter this disease. IRIC operates according to a model that is unique in Canada. Its innovative approach to research has already led to discoveries that will, over the coming years, have a significant impact on the fight against cancer. For more information: www.iric.ca.