Psoriasis is a T cell and IL-17 dependent inflammatory skin disease. Helper T cells have been assumed to be the major source of IL-17 in psoriasis but other cell types can also produce this cytokine. We immunostained human psoriatic lesions (n¼15) and healthy skin (n¼10) for IL-17A, T cells (CD4, CD8) and neutrophils (myeloperoxidase, MPO). We found that 32% of MPO+ neutrophils in psoriasis samples produced IL-17A, compared with less than 1% of total CD4 + and CD8 + cells. There were on average 10.6 IL-17A producing neutrophils per 10 high power fields in psoriasis, compared to 2.7 IL-17A producing T cells (p¼0.008). IL-17A producing neutrophils outnumbered IL-17A producing T cells four-fold demonstrating that neutrophils are an important source of IL-17A in psoriasis. To explore potential interactions between keratinocytes and neutrophils in psoriasis, we co-cultured these cells in vitro and studied neutrophil cytokine production by quantitative RT-PCR and intracellular immunostaining and flow cytometry analysis. Neutrophils co-cultured with keratinocytes upregulated production of IL-17A, IL-17F and IL-22 at both the protein and RNA levels. Neutrophils cultured with keratinocytes lost CD62L and upregulated CD11b, consistent with activation. In summary, this study suggests that neutrophils, known for long to be a part of the histologic landscape of psoriasis, are a major source of IL-17A production and have the potential to contribute to inflammation by producing IL-17F and IL-22. This is, to our knowledge, the first report that human neutrophils can produce IL-17F and IL-22.
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