The Role of Platelet–Neutrophil Interactions in Driving Autoimmune Diseases

Platelets and neutrophils are among the most abundant cell types in peripheral blood. Beyond their traditional roles in thrombosis and haemostasis, they also play an active role in modulating immune responses. Current knowledge on the role of platelet-neutrophil interactions in the immune system has been rapidly expanding. Notably, circulating platelet-neutrophil complexes (PNCs) have been widely detected in various inflammatory diseases and infections, closely associated with inflammatory processes affecting multiple organs. These findings emphasise the critical role of platelet-neutrophil interactions in driving and sustaining inflammatory responses. In this review, we elucidate the mechanisms by which neutrophils and platelets physically interact, leading to mutual activation. Additionally, activated platelets release pro-inflammatory factors that further modulate neutrophil effector functions, enhancing their immune response capabilities. We highlight the role of platelets in promoting the formation of neutrophil extracellular traps (NETs), which, in turn, promote local platelet activation, thereby exacerbating the immune response and sustaining chronic inflammation. Furthermore, we review current evidence on the role of platelet-neutrophil interactions in common autoimmune diseases such as systemic lupus erythematosus (SLE), systemic sclerosis (SSc), and rheumatoid arthritis (RA). Finally, we identify gaps in understanding the mechanisms of these interactions in the context of other autoimmune diseases and underscore the potential of targeting platelets and neutrophils as a therapeutic strategy for these conditions.