TY - JOUR
T1 - Single-Cell RNA Sequencing Reveals Cellular and Transcriptional Changes Associated With M1 Macrophage Polarization in Hidradenitis Suppurativa
AU - Mariottoni, Paula
AU - Jiang, Simon W.
AU - Prestwood, Courtney A.
AU - Jain, Vaibhav
AU - Suwanpradid, Jutamas
AU - Whitley, Melodi Javid
AU - Coates, Margaret
AU - Brown, David A.
AU - Erdmann, Detlev
AU - Corcoran, David L.
AU - Gregory, Simon G.
AU - Jaleel, Tarannum
AU - Zhang, Jennifer Y.
AU - Harris-Tryon, Tamia A.
AU - MacLeod, Amanda S.
N1 - Publisher Copyright:
© Copyright © 2021 Mariottoni, Jiang, Prestwood, Jain, Suwanpradid, Whitley, Coates, Brown, Erdmann, Corcoran, Gregory, Jaleel, Zhang, Harris-Tryon and MacLeod.
PY - 2021/8/24
Y1 - 2021/8/24
N2 - Hidradenitis suppurativa (HS) is a chronic inflammatory skin disease characterized by recurrent abscesses, nodules, and sinus tracts in areas of high hair follicle and sweat gland density. These sinus tracts can present with purulent drainage and scar formation. Dysregulation of multiple immune pathways drives the complexity of HS pathogenesis and may account for the heterogeneity of treatment response in HS patients. Using transcriptomic approaches, including single-cell sequencing and protein analysis, we here characterize the innate inflammatory landscape of HS lesions. We identified a shared upregulation of genes involved in interferon (IFN) and antimicrobial defense signaling through transcriptomic overlap analysis of differentially expressed genes (DEGs) in datasets from HS skin, diabetic foot ulcers (DFUs), and the inflammatory stage of normal healing wounds. Overlap analysis between HS- and DFU-specific DEGs revealed an enrichment of gene signatures associated with monocyte/macrophage functions. Single-cell RNA sequencing further revealed monocytes/macrophages with polarization toward a pro-inflammatory M1-like phenotype and increased effector function, including antiviral immunity, phagocytosis, respiratory burst, and antibody-dependent cellular cytotoxicity. Specifically, we identified the STAT1/IFN-signaling axis and the associated IFN-stimulated genes as central players in monocyte/macrophage dysregulation. Our data indicate that monocytes/macrophages are a potential pivotal player in HS pathogenesis and their pathways may serve as therapeutic targets and biomarkers in HS treatment.
AB - Hidradenitis suppurativa (HS) is a chronic inflammatory skin disease characterized by recurrent abscesses, nodules, and sinus tracts in areas of high hair follicle and sweat gland density. These sinus tracts can present with purulent drainage and scar formation. Dysregulation of multiple immune pathways drives the complexity of HS pathogenesis and may account for the heterogeneity of treatment response in HS patients. Using transcriptomic approaches, including single-cell sequencing and protein analysis, we here characterize the innate inflammatory landscape of HS lesions. We identified a shared upregulation of genes involved in interferon (IFN) and antimicrobial defense signaling through transcriptomic overlap analysis of differentially expressed genes (DEGs) in datasets from HS skin, diabetic foot ulcers (DFUs), and the inflammatory stage of normal healing wounds. Overlap analysis between HS- and DFU-specific DEGs revealed an enrichment of gene signatures associated with monocyte/macrophage functions. Single-cell RNA sequencing further revealed monocytes/macrophages with polarization toward a pro-inflammatory M1-like phenotype and increased effector function, including antiviral immunity, phagocytosis, respiratory burst, and antibody-dependent cellular cytotoxicity. Specifically, we identified the STAT1/IFN-signaling axis and the associated IFN-stimulated genes as central players in monocyte/macrophage dysregulation. Our data indicate that monocytes/macrophages are a potential pivotal player in HS pathogenesis and their pathways may serve as therapeutic targets and biomarkers in HS treatment.
KW - antiviral immune pathways
KW - hidradenitis suppurativa
KW - interferon
KW - macrophage-cell
KW - non-healing wounds
KW - single cell sequencing
UR - http://www.scopus.com/inward/record.url?scp=85114412767&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85114412767&partnerID=8YFLogxK
U2 - 10.3389/fmed.2021.665873
DO - 10.3389/fmed.2021.665873
M3 - Article
C2 - 34504848
AN - SCOPUS:85114412767
SN - 2296-858X
VL - 8
JO - Frontiers in Medicine
JF - Frontiers in Medicine
M1 - 665873
ER -