In the News

Dr. Christian Lood, Dr. Keith Elkon, Dr. Jeffrey Ledbetter, and visiting scientist Sabine Arve,MSc, published the article TLR7/8 activation in neutrophils impairs immune complex phagocytosis through shedding of FcgRIIA in the Journal of Experimental Medicine

Christian Lood, PhD

Neutrophils are essential to host defense. However, in SLE, circulating nucleic acid-containing immune complexes may engage neutrophils and contribute to chronic inflammation and tissue destruction. In the current investigation the Lood lab asked how these RNA-containing lupus immune complexes are sensed by neutrophils, and the particular role of the RNA component of the immune complexes in regulating subsequent neutrophil effector functions. In brief, they made the novel observation that activation of TLR7/8, the main RNA sensing receptors in neutrophils, shifted neutrophils from phagocytosis of immune complexes to the inflammatory neutrophil cell death process, NETosis, extruding its nuclear and cytosolic content causing marked inflammation and damage. These observations extend our understanding of neutrophil function in regulation of autoimmunity and inflammation, and suggest that therapeutic interventions to prevent TLR7/8 activation would increase phagocytic clearance of immune complexes while limiting their ability to induce inflammatory NETosis.