| First Author | Melki I | Year | 2021 |
| Journal | Sci Transl Med | Volume | 13 |
| Issue | 581 | PubMed ID | 33597264 |
| Mgi Jnum | J:304462 | Mgi Id | MGI:6508650 |
| Doi | 10.1126/scitranslmed.aav5928 | Citation | Melki I, et al. (2021) Platelets release mitochondrial antigens in systemic lupus erythematosus. Sci Transl Med 13(581) |
| abstractText | 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 FcgammaRIIA, a receptor for immune complexes. Because mice lack FcgammaRIIA and murine platelets are completely devoid of receptor capable of binding IgG-containing immune complexes, we used transgenic mice expressing FcgammaRIIA for our in vivo investigations. FcgammaRIIA 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 FcgammaRIIA and its cosignaling by the fibrinogen receptor alpha2bbeta3 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. |
