# Transcriptomic Profiling of Cutibacterium acnes IA1—Infected Keratinocytes Reveal Hub Genes and CLR Pathway in Acne Pathogenesis

## TL;DR

This study finds that Cutibacterium acnes IA1 affects skin cells by altering gene activity and triggering inflammation, potentially offering new targets for acne treatments.

## Contribution

The study identifies hub genes and the CLR pathway as key players in acne caused by Cutibacterium acnes IA1.

## Key findings

- 769 genes were differentially expressed in keratinocytes infected with C. acnes IA1.
- Hub genes HNRNPA2B1, HNRNPM, and RBM39 were identified as central to the response.
- The CLR pathway and increased IL-6 levels were linked to inflammation in acne pathogenesis.

## Abstract

Acne vulgaris is a prevalent chronic inflammatory skin disorder affecting over 85% of adolescents. Emerging evidence indicates that Cutibacterium acnes phylotype IA1 contributes to acne initiation and progression, yet its precise mechanisms in epidermal keratinocytes remain unclear. This study investigated C. acnes IA1’s effects on keratinocyte behavior using an in vitro HaCaT cell model. Cells were co-cultured with live C. acnes IA1 (CICC 10864) for 24 h. Transcriptomic profiling identified 769 differentially expressed genes (DEGs; adjusted p < 0.05, |log2FC| > 1), including 392 upregulated and 377 downregulated. The protein–protein interaction network analysis via Cytoscape revealed key hub genes (HNRNPA2B1, HNRNPM, RBM39). Enrichment analyses (GO, KEGG, Reactome, DO) highlighted significant involvement of the C-type lectin receptor (CLR) signaling pathway. Validation experiments showed cellular morphological changes, altered structure, and markedly elevated interleukin-6 (IL-6; p < 0.01), underscoring its role in inflammation. These findings suggest C. acnes IA1 drives acne pathogenesis by regulating hub genes that influence sebaceous gland inflammation, immune activity, and keratinocyte proliferation, positioning them as potential biomarkers for microbiome-targeted therapies. Limitations include the in vitro model’s lack of in vivo skin microenvironment complexity and use of only one representative IA1 strain.