Abstract
Abstract A rapid neutrophil response is essential for immunity against infections, however impaired elimination or migration can inflict significant tissue damage by exacerbated inflammation. Here we show that neutrophils recruited to inflamed or infected skin are rapidly redirected to skin-draining lymph nodes (dLNs) and non-draining secondary lymphoid tissues. Using transgenic mouse models and bone marrow chimeras, cutaneous inflammation is induced with imiquimod, a TLR7-mediated psoriasis-like model, or skin infection is induced by Staphylococcus aureus. We show that neutrophils migrate to the dLNs through lymphatic vessels in a CC-motif chemokine receptor 7 (CCR7)-dependent manner and are phagocytosed by resident conventional type1 dendritic cells in the dLNs when entering the lymph node, a mechanism contributing to neutrophil clearance. Deficiency of CCR7 impairs neutrophil elimination in the dLNs and leads to neutrophilic accumulation in the skin, which in turn leads to an exacerbated phenotype in a model of psoriasis-like local inflammation as well as improved clearance and immunity against cutaneous Staphylococcus aureus infection. Overall, our findings explain how impaired neutrophil migration and clearance in the dLNs could regulate cutaneous autoimmunity and infection.
Published Version
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