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Fibroblasts Produce Antimicrobial Cathelicidin in the Skin to Help Fight Acne
Targeting the fibroblast’s ability to produce cathelicidin may be a safer and better-targeted approach for treating acne.

As one of the most common skin diseases globally, acne is estimated to affect about 80 per cent of people between the ages of 11 to 30. While teenagers and young adults undergoing hormonal changes are most susceptible to acne, many people continue to struggle with this skin condition even after their 30s and beyond. The development of a pimple is known to be supported by hair follicles. However, new research by scientists at the University of California San Diego Health Sciences has found that skin cells, called fibroblasts, outside of these hair follicles could play a larger role in acne development.

“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. “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.”

Fibroblasts are the most common type of cell found in connective tissues throughout the body. They serve to secrete collagen proteins that are used to maintain the structural framework for many tissues and are known to assist wound healing. In the event of a deep tissue infection caused by bacteria, fibroblasts are triggered to differentiate into adipocytes and exhibit antimicrobial properties. However, the role of this process in non-infectious human diseases has remained elusive. Therefore, Gallo and colleagues seized the opportunity to explore the potential role of fibroblasts in acne development.

“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. “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.”

When an infection occurs within the hair follicle, the surrounding skin reacts by transforming fibroblasts into fat cells in a process called reactive adipogenesis. In addition, the antimicrobial peptide cathelicidin is also produced to help fight the infection by suppressing acne-causing bacteria.

To precisely determine the role of adipogenesis in acne, the team conducted skin biopsies on acne patients who were treated for several months with retinoids, a class of chemicals derived from vitamin A found to promote skin health. Surprisingly, the drug enhanced cathelicidin expression after treatment, demonstrating an additional, previously-unknown mechanism for why retinoids are effective in treating acne. To validate these findings, the scientists then analysed skin lesions on mice injected with the acne-causing bacteria and discovered similar treatment responses in the mice.

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

While effective in treating acne, retinoid treatments, which focus on controlling the development of lipids in skin cells, could lead to teratogenic effects, causing foetal abnormalities in pregnant women. Therefore, these drugs are only used in severe cases. With their novel findings on cathelicidin, the team hopes that their study may help advance the development of safer and better-targeted strategies for treating acne.

“This research could assist in identifying new treatment options that specifically target the fibroblast’s ability to produce cathelicidin,” said O’Neill. “Thus, creating a therapeutic for acne that would be more selective with potentially less harmful side effects.”

Source: O’Neill et al. (2022). Antimicrobial production by perifollicular dermal preadipocytes is essential to the pathophysiology of acne. Science Translational Medicine, 14(632).

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