Role of neutrophils in the imiquimod (IMQ)-induced mouse model of psoriasis

Psoriasis is a chronic skin disease associated with deregulated interplays between immune cells and keratinocytes. Neutrophil accumulation in the skin is one of the histological features that characterize psoriasis. However, the role of neutrophils in psoriasis development remains poorly understood. In this study, we utilized the imiquimod (IMQ)-induced mouse model of psoriasis to elucidate the specific contribution of neutrophils to psoriasis development. We report that neutrophils act as negative modulators of disease propagation and exacerbation by inhibiting γδ T cell effector functions via NADPH oxidase-mediated reactive oxygen species (ROS) production, as revealed by analysing disease development/progression in neutrophil-depleted mice. We also report that Syk functions as crucial molecule mediating neutrophil and γδ T cell interactions. In support of the latter findings, we demonstrate that the selective impairment of Syk-dependent signalling in neutrophils only, is sufficient to reproduce the enhancement of skin inflammation and γδ T cell infiltration observed in neutrophil-depleted mice. Overall, our findings add new insights into the specific contribution of neutrophils to disease progression in the IMQ-induced mouse model of psoriasis. Considering that, similarly to mouse psoriasis, the important role of IL-17 producing γδ T cells in human psoriasis has just started to emerge, it is likely that inhibitory crosstalk between neutrophils and γδ T cells may exist also in human psoriasis. Neutrophils may indeed act as unexpected negative players of disease development in specific types or clinical stages of human psoriasis. Consequently, also the utilization of therapeutic interventions targeted to inhibit neutrophil functions should be carefully evaluated.