期刊
ISCIENCE
卷 23, 期 10, 页码 -出版社
CELL PRESS
DOI: 10.1016/j.isci.2020.101582
关键词
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资金
- San Diego CFAR Genomics and Sequencing core
- National Institute of Arthritis and Musculoskeletal and Skin Diseases of the National Institutes of Health [K08AR067243, K08AR074556, R01AR061106]
- NIH [R01CA163336]
- VA Career Developmental Award CDA-2 [IK2BX002731]
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(+) sub-populations, 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.
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