Given the limited efficacy of clinical approaches that rely on ex vivo generated dendritic cells (DCs), it is imperative to design strategies that harness specialized DC subsets in situ. This requires delineating the expression of surface markers by DC subsets among individuals and tissues. Here, we performed a multiparametric phenotypic characterization and unbiased analysis of human DC subsets in blood, tonsil, spleen, and skin. We uncovered previously unreported phenotypic heterogeneity of human cDC2s among individuals, including variable expression of functional receptors such as CD172a. We found marked differences in DC subsets localized in blood and lymphoid tissues versus skin, and a striking absence of the newly discovered Axl⁺ DCs in the skin. Finally, we evaluated the capacity of anti-receptor monoclonal antibodies to deliver vaccine components to skin DC subsets. These results offer a promising path for developing DC subset-specific immunotherapies that cannot be provided by transcriptomic analysis alone.

鉴于依靠离体生成的树突状细胞（DC）的临床方法疗效有限，因此必须设计能够在原位利用专门化DC子集的策略。这需要通过个体和组织之间的DC子集来描述表面标志物的表达。在这里，我们对血液，扁桃体，脾脏和皮肤中的人类DC子集进行了多参数表型表征和无偏分析。我们发现了人类cDC2s以前未报告的表型异质性，包括功能受体如CD172a的可变表达。我们发现与皮肤相比，位于血液和淋巴组织中的DC子集存在明显差异，并且新发现的Axl ⁺明显缺乏皮肤中的DC。最后，我们评估了抗受体单克隆抗体将疫苗成分递送至皮肤DC亚群的能力。这些结果提供了开发DC子集特异性免疫疗法的有前途的途径，而单独通过转录组学分析不能提供。