Researchers identify two genes as key drivers of acne inflammation

Key takeaways:

• The granulin precursor gene and interleukin-13 receptor subunit alpha-1 gene are upregulated in acne lesions.
• These genes promote inflammation and hyperkeratinization.

Researchers identify two key genes that contribute to the pathogenesis of acne, potentially opening doors for new treatment approaches, according to a study.

Acne vulgaris is the most common dermatological condition worldwide with approximately 85% to 95% of adolescents experiencing acne at some point, half of which experience it into adulthood. Stopping acne early on can mitigate troubling sequelae such as post-inflammatory hyperpigmentation and scarring, Min Deng, a postdoctoral scholar at the David Geffen School of Medicine at the University of California, Los Angeles, and colleagues wrote.

“This project aims to identify key dysregulated genes and signaling pathways common to all acne patients, especially in the early stages of papule formation,” Deng told Healio.

Using high-resolution spatial RNA sequencing, Deng and colleagues analyzed active acne lesions in six subjects and compared these lesions with the skin of healthy individuals.

What they found is that there are two key genes that are upregulated in acne lesions compared with healthy skin. These genes are GRN, the granulin precursor gene, and IL13RA1, the interleukin-13 receptor subunit alpha-1 gene, both of which are key drivers of inflammation and hyperkeratinization.

“Inflammation driven by immune cells and hyperkeratinization of keratinocytes are two critical processes in the initiation and development of acne,” Deng said. “The upregulation of GRN and IL13RA1 in acne patients exacerbates inflammation and promotes hyperkeratinization.”

According to the study, GRN increased the expression of proinflammatory cytokines and chemokines, including IL-18, CCL5 and CXCL2 in TREM2 macrophages, whereas IL13RA1 promoted the dysregulation of genes associated with hyperkeratinization by IL-13 in HaCaT cells.

“This is the first study to establish the functions of these two genes in acne, shedding light on new mechanisms of acne pathogenesis,” Deng said. “Targeting these genes and their associated pathways could pave the way for new treatments, benefiting the more than 85% of teenagers affected by acne, ultimately helping them build confidence and improve their quality of life during this critical period.”

For more information:

Min Deng can be reached at MinDeng@mednet.ucla.edu.