Neutrophil extracellular traps activate lymphocytes in systemic lupus erythematosus

The aberrant activation of lymphocytes caused by autoantigens plays a critical role in the pathogenesis of systemic lupus erythematosus (SLE). A large number of autoantigens are released during the formation of neutrophil extracellular traps (NETs), but their pathogenic mechanism in SLE has not been fully elucidated. We therefore investigated the role of NETs by activating lymphocytes in SLE.

Peripheral venous blood samples from 58 patients with SLE and 54 healthy controls were included in this study, and the activated indicators of lymphocytes (HLA-DR and CD69) were analysed by flow cytometry. The NETs levels were quantified and their correlation with the levels of activated lymphocytes were analysed. Polymorphonuclear neutrophils (PMNs) and peripheral blood mononuclear cells (PBMCs) were isolated via gradient density separation. The PMNs were stimulated using phorbol 12-myristate 13-acetate (PMA) to form NETs following incubation with autologous PBMCs. The activation of the lymphocytes was tested via flow cytometry.

The elevated expression of HLA-DR and CD69 on CD4+ T and CD19+ B cells was observed in the patients with SLE and positively correlated with the NETs level (p<0.05). In contrast to the control group, the NETs group directly activated the CD4+ T and CD19+ B lymphocytes in vitro by increasing the expression of HLA-DR and CD69 (p<0.05).

NETs induced the abnormal activation of T and B lymphocytes, which participated in the pathogenesis of SLE. This finding revealed the synergistic roles of innate immunity mediated by neutrophils and adaptive immunity mediated by lymphocytes.