PDF(Pubmed)
Abstract：
Inflammatory skin diseases including atopic dermatitis (AD) and psoriasis (PSO) are underpinned by dendritic cell (DC)-mediated T cell responses. Currently, the heterogeneous human cutaneous DC population is incompletely characterized, and its contribution to these diseases remains unclear. Here, we performed index-sorted single-cell flow cytometry and RNA sequencing of lesional and nonlesional AD and PSO skin to identify macrophages and all DC subsets, including the newly described mature LAMP3+BIRC3+ DCs enriched in immunoregulatory molecules (mregDC) and CD14+ DC3. By integrating our indexed data with published skin datasets, we generated a myeloid cell universe of DC and macrophage subsets in healthy and diseased skin. Importantly, we found that CD14+ DC3s increased in PSO lesional skin and co-produced IL1B and IL23A, which are pathological in PSO. Our study comprehensively describes the molecular characteristics of macrophages and DC subsets in AD and PSO at single-cell resolution, and identifies CD14+ DC3s as potential promoters of inflammation in PSO.
摘要：
包括特应性皮炎(AD)和牛皮癣(PSO)的炎性皮肤病由树突状细胞(DC)介导的T细胞应答支持。目前,异质人类皮肤DC群体的特征不完全，其对这些疾病的贡献尚不清楚。这里,我们对病变和非病变AD和PSO皮肤进行了指数分选的单细胞流式细胞术和RNA测序，以鉴定巨噬细胞和所有DC亚群，包括新描述的富含免疫调节分子(mregDC)和CD14+DC3的成熟LAMP3+BIRC3+DC。通过将我们的索引数据与已发布的皮肤数据集集成，我们在健康和患病皮肤中产生了DC和巨噬细胞亚群的骨髓细胞。重要的是,我们发现CD14+DC3s在PSO病变皮肤中增加，并共同产生IL1B和IL23A，在PSO中是病理性的。我们的研究以单细胞分辨率全面描述了AD和PSO中巨噬细胞和DC亚群的分子特征，并鉴定CD14+DC3s是PSO炎症的潜在启动子。
