Profibrotic Subsets of SPP1+ Macrophages and POSTN+ Fibroblasts Contribute to Fibrotic Scarring in Acne Keloidalis

Yi Kai Hong, Daw Yang Hwang, Chao Chun Yang, Siao Muk Cheng, Peng Chieh Chen, Wilson Jr Aala, Hans I-Chen Harn, Spencer T. Evans, Alexandros Onoufriadis, Si Lin Liu, Yu Chen Lin, Yi Han Chang, Tzu Kun Lo, Kuo Shu Hung, Yi Chao Lee, Ming Jer Tang, Kurt Q. Lu, John A. McGrath, Chao Kai Hsu

Research output: Contribution to journalArticlepeer-review

4 Citations (Scopus)

Abstract

Acne keloidalis is a primary scarring alopecia characterized by longstanding inflammation in the scalp causing keloid-like scar formation and hair loss. Histologically, acne keloidalis is characterized by mixed leukocytic infiltrates in the acute stage followed by a granulomatous reaction and extensive fibrosis in the later stages. To further explore its pathogenesis, bulk RNA sequencing, single-cell RNA sequencing, and spatial transcriptomics were applied to occipital scalp biopsy specimens of lesional and adjacent no-lesional skin in patients with clinically active disease. Unbiased clustering revealed 19 distinct cell populations, including 2 notable populations: POSTN+ fibroblasts with enriched extracellular matrix signatures and SPP1+ myeloid cells with an M2 macrophage phenotype. Cell communication analyses indicated that fibroblasts and myeloid cells communicated by SPP1 signaling networks in lesional skin. A reverse transcriptomics in silico approach identified corticosteroids as possessing the capability to reverse the gene expression signatures of SPP1+ myeloid cells and POSTN+ fibroblasts. Intralesional corticosteroid injection greatly reduced SPP1 and POSTN gene expression as well as acne keloidalis disease activity. Spatial transcriptomics and immunofluorescence staining verified microanatomic specificity of SPP1+ myeloid cells and POSTN+ fibroblasts with disease activity. In summary, the communication between POSTN+ fibroblasts and SPP1+ myeloid cells by SPP1 axis may contribute to the pathogenesis of acne keloidalis.

Original languageEnglish
Pages (from-to)1491-1504.e10
JournalJournal of Investigative Dermatology
Volume144
Issue number7
DOIs
Publication statusPublished - 2024 Jul

All Science Journal Classification (ASJC) codes

  • Biochemistry
  • Molecular Biology
  • Dermatology
  • Cell Biology

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