Neutrophils are cells of the immune system, essential for fighting bacterial and fungal infections. Within the human bone marrow, one million neutrophils are generated every second, a rapid and complex process requiring substantial energy and key to the body’s immune response to infection. However, the mechanisms that regulate this process are not fully understood, and dysfunctional neutrophil differentiation can lead to disease.
In their latest publication in Immunity, Researchers at the Simon and Jacobsen labs at the MRC WIMM (Radcliffe Department of Medicine) and Kennedy Institute (Nuffield Department of Orthopaedics, Rheumatology and Musculoskeletal Sciences) report that autophagy, an intracellular self-eating process, is necessary for successful neutrophil differentiation. Through autophagy, neutrophil precursor cells are able to degrade lipid droplets, which releases fatty acids. This allows a metabolic switch from glycolysis to free fatty acid oxidation, which the researchers have shown to be essential for neutrophil maturation.
Many myeloid leukemias are characterised by defective differentiation and precursor cell accumulation, and autophagy defects have been reported. The next goal for the researchers is to test whether a metabolic rewiring dependent on autophagy similar to that observed in neutrophils may also take place in acute myebloastic leukemias.
Find out more:
Riffelmacher T., et al (2017) Autophagy-Dependent Generation of Free Fatty Acids Is Critical for Normal Neutrophil Differentiation, Immunity, 47 466-480