Acne

New discovery in acne pathogenesis may lead to novel treatments


The discovery of a specific antimicrobial-producing fibroblast outside the sebaceous follicle and the key role it plays in acne development could result in more targeted treatment options, according to US researchers.

New insights into the potential role of ‘reactive adipogenesis’ by dermal fibroblasts in acne have been made by a team of scientists and dermatologists at UC San Diego School of Medicine.

In findings published in the journal Science Translational Medicine the researchers described how adipogenesis in response to sebaceous follicle infection by C. acnes resulted in fibroblasts transforming into adipocytes and producing an antimicrobial peptide called cathelicidin.

In animal and human in vitro models they showed that C. acnes triggered the production of cathelicidin in preadipocyte cells,  mediated by Toll-like receptor 2 (TLR2).

They also showed that treatment with retinoids suppressed the capacity of C. acnes to form acne-like lesions, inhibited adipogenesis, and enhanced cathelicidin expression in preadipocytes.

Analysis of biopsies of inflamed skin of acne patients after retinoid treatment also showed enhanced induction of cathelicidin, which the researchers said was a previously unknown beneficial effect of retinoids in difficult-to-treat acne.

“Overall, these data provide evidence that adipogenic fibroblasts are a critical component of the pathogenesis of acne and represent a potential target for therapy,” they wrote.

“These findings may transform the way we treat acne,” said senior author Professor Richard Gallo, chair of the Department of Dermatology at UC San Diego.

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

Lead author Dr Alan O’Neill (PhD) said the discovery of cathelicidin’s role came as a surprise.

“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,” he said.

“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 C. acnes.”

The research could assist in identifying new treatment options that specifically target the fibroblast’s ability to produce cathelicidin, bypassing the retinoid pathway that is related to adverse effects such as teratogenesis, said Dr O’Neill.

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