IL-23-activation of IL-17 producing T cells is involved in many rheumatic diseases. Herein, we investigate the role of IL-23 in the activation of myeloid cell subsets that contribute to skin inflammation in mice and man. IL-23 gene transfer in WT, IL-23R reporter mice and subsequent analysis with spectral cytometry show that IL-23 regulates early innate immune events by inducing the expansion of a myeloid MDL1CD11bLy6G population that dictates epidermal hyperplasia, acanthosis, and parakeratosis; hallmark pathologic features of psoriasis. Genetic ablation of MDL-1, a major PU.1 transcriptional target during myeloid differentiation exclusively expressed in myeloid cells, completely prevents IL-23-pathology. Moreover, we show that IL-23-induced myeloid subsets are also capable of producing IL-17A and IL-23RMDL1 cells are present in the involved skin of psoriasis patients and gene expression correlations between IL-23 and MDL-1 have been validated in multiple patient cohorts. Collectively, our data demonstrate a novel role of IL-23 in MDL-1-myelopoiesis that is responsible for skin inflammation and related pathologies. Our data open a new avenue of investigations regarding the role of IL-23 in the activation of myeloid immunoreceptors and their role in autoimmunity.

中文翻译：

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IL-23 诱导 CLEC5A+ IL-17A+ 中性粒细胞并引发与银屑病关节炎相关的皮肤炎症

产生 IL-17 的 T 细胞的 IL-23 激活与许多风湿性疾病有关。在此，我们研究了 IL-23 在激活导致小鼠和人类皮肤炎症的骨髓细胞亚群中的作用。 WT、IL-23R 报告小鼠中的 IL-23 基因转移以及随后的光谱细胞术分析表明，IL-23 通过诱导骨髓 MDL1CD11bLy6G 群体的扩张来调节早期先天免疫事件，从而导致表皮增生、棘皮症和角化不全；银屑病的标志性病理特征。 MDL-1（骨髓分化期间仅在骨髓细胞中表达的主要 PU.1 转录靶标）的基因消除可完全预防 IL-23 病理学。此外，我们发现 IL-23 诱导的骨髓亚群也能够产生 IL-17A，并且 IL-23RMDL1 细胞存在于银屑病患者的受累皮肤中，并且 IL-23 和 MDL-1 之间的基因表达相关性已在多个患者队列。总的来说，我们的数据证明了 IL-23 在 MDL-1 骨髓细胞生成中的新作用，MDL-1 骨髓细胞生成是皮肤炎症和相关病理的原因。我们的数据为研究 IL-23 在髓系免疫受体激活中的作用及其在自身免疫中的作用开辟了新途径。