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Single-Cell Profiling Reveals Divergent, Globally Patterned Immune Responses in Murine Skin Inflammation (RNA - ADT - Immune - Figure 1)

Yale Liu, Christopher Cook, Andrew J Sedgewick, Shuyi Zhang, Marlys S Fassett, Roberto R Ricardo-Gonzalez, Paymann Harirchian, Sakeen W Kashem, Sho Hanakawa, Jacob R Leistico, Jeffrey P North, Mark A Taylor, Wei Zhang, Mao-Qiang Man, Alexandra Charruyer, Nadejda Beliakova-Bethell, Stephen C Benz, Ruby Ghadially, Theodora M Mauro, Daniel H Kaplan, Kenji Kabashima, Jaehyuk Choi, Jun S Song, Raymond J Cho, Jeffrey B Cheng

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.

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Species: mouse
Number of cells: 44130
Number of downloads: 6
Study size: 1GB
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Immunology 
Skin 
Inflammation 
Oxazolone 
Imiquimod