iScience (Oct 2020)
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. Kaplan,
- Kenji Kabashima,
- Jaehyuk Choi,
- Jun S. Song,
- Raymond J. Cho,
- Jeffrey B. Cheng
Affiliations
- Yale Liu
- Department of Dermatology, University of California, San Francisco, San Francisco, CA, USA; Dermatology Service, San Francisco Veterans Administration Health Care System, San Francisco, CA, USA; Department of Dermatology, the Second Affiliated Hospital of Xi'an Jiaotong University, ShaanXi, China
- Christopher Cook
- Department of Dermatology, University of California, San Francisco, San Francisco, CA, USA; Dermatology Service, San Francisco Veterans Administration Health Care System, San Francisco, CA, USA
- Andrew J. Sedgewick
- ImmunityBio Inc, Culver City, CA, USA
- Shuyi Zhang
- Department of Physics, Carl R. Woese Institute for Genomic Biology, University of Illinois at Urbana-Champaign, Champaign, IL, USA
- Marlys S. Fassett
- Department of Dermatology, University of California, San Francisco, San Francisco, CA, USA; Department of Immunology and Microbiology, University of California, San Francisco, San Francisco, CA, USA
- Roberto R. Ricardo-Gonzalez
- Department of Dermatology, University of California, San Francisco, San Francisco, CA, USA; Department of Immunology and Microbiology, University of California, San Francisco, San Francisco, CA, USA
- Paymann Harirchian
- Department of Dermatology, University of California, San Francisco, San Francisco, CA, USA; Dermatology Service, San Francisco Veterans Administration Health Care System, San Francisco, CA, USA
- Sakeen W. Kashem
- Department of Dermatology, University of California, San Francisco, San Francisco, CA, USA
- Sho Hanakawa
- Department of Dermatology, Kyoto University Graduate School of Medicine, Kyoto, Japan
- Jacob R. Leistico
- Department of Physics, Carl R. Woese Institute for Genomic Biology, University of Illinois at Urbana-Champaign, Champaign, IL, USA
- Jeffrey P. North
- Department of Dermatology, University of California, San Francisco, San Francisco, CA, USA
- Mark A. Taylor
- Department of Dermatology, University of California, San Francisco, San Francisco, CA, USA
- Wei Zhang
- Dermatology Service, San Francisco Veterans Administration Health Care System, San Francisco, CA, USA
- Mao-Qiang Man
- Dermatology Service, San Francisco Veterans Administration Health Care System, San Francisco, CA, USA
- Alexandra Charruyer
- Department of Dermatology, University of California, San Francisco, San Francisco, CA, USA; Dermatology Service, San Francisco Veterans Administration Health Care System, San Francisco, CA, USA
- Nadejda Beliakova-Bethell
- Department of Medicine, University of California San Diego, La Jolla, CA 92093-0679, USA; Veterans Affairs Medical Center, San Diego, CA, USA
- Stephen C. Benz
- ImmunityBio Inc, Culver City, CA, USA
- Ruby Ghadially
- Dermatology Service, San Francisco Veterans Administration Health Care System, San Francisco, CA, USA
- Theodora M. Mauro
- Dermatology Service, San Francisco Veterans Administration Health Care System, San Francisco, CA, USA
- Daniel H. Kaplan
- Departments of Dermatology and Immunology, University of Pittsburgh, Pittsburgh, PA, USA
- Kenji Kabashima
- Department of Dermatology, Kyoto University Graduate School of Medicine, Kyoto, Japan; Singapore Immunology Network (SIgN) and Skin Research Institute of Singapore (SRIS), Agency for Science, Technology and Research (A∗STAR), Singapore, Singapore
- Jaehyuk Choi
- Department of Dermatology, Northwestern School of Medicine, Chicago, IL, USA
- Jun S. Song
- Department of Physics, Carl R. Woese Institute for Genomic Biology, University of Illinois at Urbana-Champaign, Champaign, IL, USA
- Raymond J. Cho
- Department of Dermatology, University of California, San Francisco, San Francisco, CA, USA; Corresponding author
- Jeffrey B. Cheng
- Department of Dermatology, University of California, San Francisco, San Francisco, CA, USA; Dermatology Service, San Francisco Veterans Administration Health Care System, San Francisco, CA, USA; Corresponding author
- Journal volume & issue
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Vol. 23,
no. 10
p. 101582
Abstract
Summary: 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.
