Spatial Mass Cytometry-Based Single-Cell Imaging Reveals a Disrupted Epithelial-Immune Axis in Prurigo Nodularis

Jay Patel; Junwen Deng; Anusha Kambala; Kevin K Lee; Hannah L Cornman; Varsha Parthasarathy; Thomas Pritchard; Shihua Chen; Alexei G Hernandez; Sarah Shin; Olusola O Oladipo; Madan M Kwatra; Won Jin Ho; Shawn G Kwatra

doi:10.1016/j.jid.2024.01.036

Spatial Mass Cytometry-Based Single-Cell Imaging Reveals a Disrupted Epithelial-Immune Axis in Prurigo Nodularis

J Invest Dermatol. 2024 Mar 24:S0022-202X(24)00202-1. doi: 10.1016/j.jid.2024.01.036. Online ahead of print.

Authors

Affiliations

¹ Department of Dermatology, University of Maryland School of Medicine, Baltimore, Maryland, USA; Maryland Itch Center, University of Maryland School of Medicine, Baltimore, Maryland, USA; Department of Dermatology, University of Rochester, Rochester, New York, USA.
² Department of Dermatology, Albert Einstein College of Medicine, Bronx, New York, USA.
³ The George Washington University School of Medicine and Health Sciences, Washington, DC, USA.
⁴ Department of Dermatology, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA.
⁵ Department of Dermatology, University of Maryland School of Medicine, Baltimore, Maryland, USA; Maryland Itch Center, University of Maryland School of Medicine, Baltimore, Maryland, USA.
⁶ Department of Oncology, Johns Hopkins University School of Medicine, Baltimore, Maryland.
⁷ Department of Anesthesiology, Duke University School of Medicine, Durham, North Carolina, USA.
⁸ Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University, Baltimore, Maryland, USA; Convergence Institute, Johns Hopkins University, Baltimore, Maryland, USA; Mass Cytometry Facility, Johns Hopkins University, Baltimore, Maryland, USA.
⁹ Department of Dermatology, University of Maryland School of Medicine, Baltimore, Maryland, USA; Maryland Itch Center, University of Maryland School of Medicine, Baltimore, Maryland, USA. Electronic address: kwatra.shawn@gmail.com.

PMID: 38522569
DOI: 10.1016/j.jid.2024.01.036

Abstract

Prurigo nodularis (PN) is a chronic, inflammatory skin condition that disproportionately affects African Americans and features intensely pruritic, hyperkeratotic nodules on the extremities and trunk. PN is understudied compared with other inflammatory skin diseases, with the spatial organization of the cutaneous infiltrate in PN yet to be characterized. In this work, we employ spatial imaging mass cytometry to visualize PN lesional skin inflammation and architecture with single-cell resolution through an unbiased machine learning approach. PN lesional skin has increased expression of caspase 3, NF-kB, and phosphorylated signal transducer and activator of transcription 3 compared with healthy skin. Keratinocytes in lesional skin are subdivided into CD14+CD33+, CD11c+, CD63+, and caspase 3-positive innate subpopulations. CD14+ macrophage populations expressing phosphorylated extracellular signal-regulated kinase 1/2 correlate positively with patient-reported itch (P = .006). Hierarchical clustering reveals a cluster of patients with PN with greater atopy, increased NF-kB+ signal transducer and activator of transcription 3-positive phosphorylated extracellular signal-regulated kinase 1/2-positive monocyte-derived myeloid dendritic cells, and increased vimentin expression (P < .05). Neighborhood analysis finds interactions between CD14+ macrophages, CD3+ T cells, monocyte-derived myeloid dendritic cells, and keratinocytes expressing innate immune markers. These findings highlight phosphorylated extracellular signal-regulated kinase-positive CD14+ macrophages as contributors to itch and suggest an epithelial-immune axis in PN pathogenesis.

Keywords: Biomarkers; Imaging mass cytometry; Prurigo nodularis; Single cell; Translational.