Single-Cell Profiling Reveals Divergent, Globally Patterned Immune Responses in Murine Skin Inflammation

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. KaplanKenji Kabashima, Jaehyuk Choi, Jun S. Song, Raymond J. Cho*, Jeffrey B. Cheng

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

Abstract

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.

Original languageEnglish (US)
Article number101582
JournaliScience
Volume23
Issue number10
DOIs
StatePublished - Oct 23 2020

Keywords

  • Immunology
  • Systems Biology

ASJC Scopus subject areas

  • General

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