Inflammatory response heterogeneity has impeded high-resolution dissection of diverse immune cell populations during activation. We characterize mouse cutaneous immune cells by single-cell RNA sequencing, after inducing inflammation using imiquimod and oxazolone dermatitis models. We identify 13 CD45⁺ subpopulations, which broadly represent most functionally characterized immune cell types. Oxazolone pervasively upregulates Jak2/Stat3 expression across T cells and antigen-presenting cells (APCs). Oxazolone also induces Il4/Il13 expression in newly infiltrating basophils, and Il4ra and Ccl24, most prominently in APCs. In contrast, imiquimod broadly upregulates Il17/Il22 and Ccl4/Ccl5. A comparative analysis of single-cell inflammatory transcriptional responses reveals that APC response to oxazolone is tightly restricted by cell identity, whereas imiquimod enforces shared programs on multiple APC populations in parallel. These global molecular patterns not only contrast immune responses on a systems level but also suggest that the mechanisms of new sources of inflammation can eventually be deduced by comparison to known signatures.

炎症反应异质性阻碍了激活过程中各种免疫细胞群体的高分辨率解剖。我们使用咪喹莫特和恶唑酮皮炎模型诱发炎症后，通过单细胞RNA测序表征小鼠皮肤免疫细胞。我们确定了13个CD45 ⁺亚群，广泛代表了功能最强大的免疫细胞类型。恶唑酮普遍上调跨T细胞和抗原呈递细胞（APC）的Jak2 / Stat3表达。恶唑酮也诱导IL-4 / IL-13的表达在新浸润嗜碱性粒细胞和Il4ra和CCL24，在APC中最为突出。相反，咪喹莫特广泛上调Il17 / Il22和Ccl4 / Ccl5。对单细胞炎症转录反应的比较分析表明，对恶唑酮的APC反应受到细胞身份的严格限制，而咪喹莫特在多个APC群体上并行执行共享程序。这些整体分子模式不仅在系统水平上对比了免疫应答，而且表明与已知特征相比，最终可以推断出新的炎症来源的机制。