@article{4c7bfd0abb9b49ddb415b919c3b24f58,
title = "Single-Cell Profiling Reveals Divergent, Globally Patterned Immune Responses in Murine Skin Inflammation",
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.",
keywords = "Immunology, Systems Biology",
author = "Yale Liu and Christopher Cook and Sedgewick, {Andrew J.} and Shuyi Zhang and Fassett, {Marlys S.} and Ricardo-Gonzalez, {Roberto R.} and Paymann Harirchian and Kashem, {Sakeen W.} and Sho Hanakawa and Leistico, {Jacob R.} and North, {Jeffrey P.} and Taylor, {Mark A.} and Wei Zhang and Man, {Mao Qiang} and Alexandra Charruyer and Nadejda Beliakova-Bethell and Benz, {Stephen C.} and Ruby Ghadially and Mauro, {Theodora M.} and Kaplan, {Daniel H.} and Kenji Kabashima and Jaehyuk Choi and Song, {Jun S.} and Cho, {Raymond J.} and Cheng, {Jeffrey B.}",
note = "Funding Information: We acknowledge Rachel M. Sevey for critical assistance in scientific graphic design, Paola DiMeglio for assistance in antibody selection, and support from the San Diego CFAR Genomics and Sequencing core. This project was supported in part by National Institute of Arthritis and Musculoskeletal and Skin Diseases of the National Institutes of Health K08AR067243 to J.B.C., K08AR074556 to M.S.F., R01AR061106 to T.M.M. (administered by the Northern California Institute for Research and Education), NIH R01CA163336 to J.S.S., and VA Career Developmental Award CDA-2 (IK2BX002731) to N.B.B. This content is solely the responsibility of the authors and does not necessarily represent the official views of either the National Institutes of Health or the Department of Veterans Affairs. Funding Information: We acknowledge Rachel M. Sevey for critical assistance in scientific graphic design, Paola DiMeglio for assistance in antibody selection, and support from the San Diego CFAR Genomics and Sequencing core. This project was supported in part by National Institute of Arthritis and Musculoskeletal and Skin Diseases of the National Institutes of Health K08AR067243 to J.B.C. K08AR074556 to M.S.F. R01AR061106 to T.M.M. (administered by the Northern California Institute for Research and Education), NIH R01CA163336 to J.S.S. and VA Career Developmental Award CDA-2 (IK2BX002731) to N.B.B. This content is solely the responsibility of the authors and does not necessarily represent the official views of either the National Institutes of Health or the Department of Veterans Affairs. R.J.C. and J.B.C. designed the study. Y.L. C.C. P.H. W.Z. M.S.F. and R.R.G. performed sample preparation and analysis. Y.L, C.C. A.J.S. S.Z. M.A.T. J.L. N.B.-B. S.C.B. and J.S.S. performed computational analyses. J.P.N. performed microscopy analyses. Y.L, C.C. R.J.C. and J.B.C. wrote the manuscript with contributions from A.J.S. S.Z. M.S.F, R.R.R.-G. P.H. S.W.K. S.H. J.R.L. J.P.N. M.A.M, W.Z. M.-Q.M. T.M.M. A.C. N.B. S.C.B. R.G. D.H.K. K.K. J.C. and J.S.S. A.J.S. and S.C.B. are employees of ImmunityBio Inc, S.C.B. is an equity holder of ImmunityBio Inc. The remaining authors disclose no conflicts. Publisher Copyright: {\textcopyright} 2020",
year = "2020",
month = oct,
day = "23",
doi = "10.1016/j.isci.2020.101582",
language = "English (US)",
volume = "23",
journal = "iScience",
issn = "2589-0042",
publisher = "Elsevier Inc.",
number = "10",
}