Genetics

New research may help improve treatment

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A new study found that atopic dermatitis, such as eczema, may develop differently than previously thought. wendy laurel / Stocksy
  • A dental researcher at the University of Pennsylvania noted the presence of skin lesions similar to atopic dermatitis during a study with mice.
  • Researchers found that atopic dermatitis may develop differently than previously thought.
  • The researchers learned that fibroblast dysregulation contributes to atopic dermatitis development through RNA analysis.
  • This revelation still needs more research, but it has the potential to shape the development of new atopic dermatitis treatments.

A new study published in the journal Science Translational Medicine presents new insight into how atopic dermatitis (AD) develops. The study examined the appearance of lesions in genetically modified mice because the lesions were similar to how AD presents in humans.

Researchers from the University of Pennsylvania and the University of Tennessee did RNA analysis on both the modified mice and human samples and found some similarities.

RNA, or ribonucleic acid, is found in all living cells. It is the messenger that carries instructions from DNA.

The human body uses RNA to construct cells, respond to immune challenges, and carry proteins from one part of the cell to another, according to Shurjo K. Sen, Ph.D.program director at the National Human Genome Research Institute.

Researchers often conduct RNA analysis to study gene expression. It is an essential tool for molecular diagnostics, such as assessing cancer and detecting viruses like HIV.

Using RNA analysis, the researchers created a monoclonal antibody treatment and saw improvement in the mice.

According to the American Academy of Dermatology Association, AD is a common skin condition affecting children and adults. Approximately 1 out of 10 Americans have AD, which is considered an inflammatory disease.

Some signs and symptoms of atopic dermatitis, which is also known as eczema, include:

  • Dry, scaly, itchy skin
  • Flushed skin
  • Skin with oozing or leaking fluid

This skin condition presently cannot be cured, but there are some treatments available that may help control the severity of the condition.

Kang Ko, a student at the University of Pennsylvania’s dental program, examined inflammatory signaling in mice when he noticed something unusual.

The mice Ko was working with were designed to lack the Ikkb gene responsible for activating NF-KB signaling. According to the authors, NF-KB is “a master inflammatory transcription factor that regulates immune-responsive genes.”

Ko and the other researchers were surprised when the mice developed lesions, given how NF-KB functions.

“The affected skin demonstrated hair loss, thickening, scaling, erythema, or focal crusting with scab formation,” the study authors wrote.

“That was interesting to us because these ulcerations looked like an inflammatory event, but we had effectively turned off the activity of NF-KB, which should reduce inflammation,” said Dr. Dana Graves. “So this was a paradox.”

Graves, a co-author of the paper, is a professor at Penn Dental Medicine and oversaw the lab Ko used for research.

Ko notified Dr. John Seykora, a dermatology professor at the university’s Perelman School of Medicine, about the findings. They then collaborated with researchers at the University of Tennessee to continue the research.

The researchers decided the next step in learning why skin lesions were present despite the mice lacking NF-KB was to do an RNA analysis on the mice.

Fibroblasts are cells that are part of the connective-tissue family that “help maintain the structural framework of tissues.” Through the RNA analysis, the researchers learned that fibroblasts factored into the lesion development.

In the fibroblasts without the Ikkb gene, a domain transcription factor called CEBPB was activated. CCL11, a chemokine that contributes to inflammation, was also overexpressed.

Next, the scientists compared the RNA analysis to an analysis in human samples and found similar results. The authors write that the RNA analysis suggests “a potential role of these cells in the pathogenesis of inflammatory skin disorders.”

“We worked out the mechanism in the mouse, then showed that much of it applied to human tissue as well,” said Seykora.

This study provides insight into how AD develops, but it also has the potential to lead to the development of new treatments.

The researchers used a monoclonal antibody treatment that targeted CCL11 in 2-week-old mice, which reduced the inflammation response.

“This study highlights a previously unrecognized molecular pathway in skin cells that can lead to a TH2 immune response in the skin,” Dr. Adam Mamelak said in an interview with Medical News Today.

Mamelak is a board certified dermatologist and owner of the Austin Mohs Surgery Center in Austin, Texas.

He noted how dysregulation in the fibroblast cells recruited inflammatory cells. “This was observed in the lab in both mouse and human models for atopic dermatitis. Furthermore, inhibiting CCL11 in the mouse model was able to reduce the type of inflammation seen in AD, ”Mamelak said.

“As we continue to unravel the cause and mechanism of action of atopic eczema and search for better treatments, these investigators have drawn our attention to a previously unrecognized piece of the puzzle,” said Mamelak. “CCL11 may serve to become another target for drugs and therapies designed to treat and cure atopic dermatitis.”

Dr. Geeta Yadav, a board certified dermatologist and founder of Skin Science Dermatology in Toronto, Canada, also spoke with MNT about the study.

“In this study, mice that had a specific gene deletion – Ikkb – were prone to atopic dermatitis despite controlling for environmental factors, ”Yadav said. “This new data showing CCL11’s role in AD may also be an important pathway in the development of new treatments for AD.”

“The authors noted that blocking CCL11 reduced the immune responses associated with atopic dermatitis… and therefore could be another therapeutic target for AD in the future,” Yadav said.

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