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Anti-microbial peptide influences acne pathogenesis

New research suggests that while hair follicles do contribute to the development of acne, adipogenic fibroblasts outside of hair follicles are a more critical component in the pathogenesis of acne than previously believed.

According to this study from the University of California, San Diego, cathelicidin, an antimicrobial peptide produced by fibroblasts, is important in the development of acne even when hair follicles are not involved. The study was published in the Feb. 16, 2022 issue of Science Translational Medicine.

“These findings may transform the way we treat acne,” said Richard Gallo, MD, PhD, Ima Gigli Distinguished Professor of Dermatology and chair of the Department of Dermatology at UC San Diego School of Medicine in a press release.

“Previously, it was thought that hair follicles were most important for acne to develop. In this study, we looked at the cells outside of the hair follicle and found they had a major effect on controlling bacteria and the development of acne.”

To counter an infection within a hair follicle, the surrounding fibroblasts undergo reactive adipogenesis and are transformed into fat cells. Cathelicidin is also produced by the fibroblasts to help counter infection and suppress the bacteria that can cause Cutibacterium acnes.

In the study, the research team performed skin biopsies on acne patients treated for several months with retinoids. Their results showed retinoids enhanced the expression of cathelicidin, identifying a previously unknown mechanism helping to explain why retinoids are beneficial in the treatment of acne. They also observed a similar response in mouse studies.

While retinoids are effective for acne, they are teratogenic and produce other side effects. These findings may help to develop a more targeted approach to acne treatment.

“We began our research wanting to understand the biology of acne and specifically looked at the role of fibroblasts, which typically provide structural support in the deeper layers of the skin,” said first author Alan O’Neill, PhD, project scientist at UC San Diego School of Medicine in the press release. “What we uncovered instead was that these cells were activated to produce large amounts of an important antimicrobial, cathelicidin, in response to acne-causing bacteria called Cutibacterium acnes.”

Added Dr. Gallo: “Cathelicidin being so highly expressed in acne biopsy tissue was a very interesting finding to us. Knowing this will be helpful in developing a more targeted therapy to treat acne.”


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