[Research Articles] Platelets release mitochondrial antigens in systemic lupus erythematosus

The accumulation of DNA and nuclear components in blood and their recognition by autoantibodies play a central role in the pathophysiology of systemic lupus erythematosus (SLE). Despite the efforts, the sources of circulating autoantigens in SLE are still unclear. Here, we show that in SLE, platelets release mitochondrial DNA, the majority of which is associated with the extracellular mitochondrial organelle. Mitochondrial release in patients with SLE correlates with platelet degranulation. This process requires the stimulation of platelet FcRIIA, a receptor for immune complexes. Because mice lack FcRIIA and murine platelets are completely devoid of receptor capable of binding IgG-containing immune complexes, we used transgenic mice expressing FcRIIA for our in vivo investigations. FcRIIA expression in lupus-prone mice led to the recruitment of platelets in kidneys and to the release of mitochondria in vivo. Using a reporter mouse with red fluorescent protein targeted to the mitochondrion, we confirmed platelets as a source of extracellular mitochondria driven by FcRIIA and its cosignaling by the fibrinogen receptor α2bβ3 in vivo. These findings suggest that platelets might be a key source of mitochondrial antigens in SLE and might be a therapeutic target for treating SLE.

Source: Science Translational Medicine - February 17, 2021 Category: Biomedical Science Authors: Melki, I., Allaeys, I., Tessandier, N., Levesque, T., Cloutier, N., Laroche, A., Vernoux, N., Becker, Y., Benk-Fortin, H., Zufferey, A., Rollet-Labelle, E., Pouliot, M., Poirier, G., Patey, N., Belleannee, C., Soulet, D., McKenzie, S. E., Brisson, A., Tre Tags: Research Articles Source Type: research