A mother’s intuition and scientific eye sparked the discovery of a possible mechanism for infant eczema.

The new findings, published in Nature, show that skin dendritic cells — responsible for processing pathogens and presenting them to the immune system — are hyperreactive in infancy. According to a series of mouse experiments led by Mount Sinai researchers, the cells mount an outsized response to dust mites, fungi, and other allergens that adult skin cells typically ignore.

“This paper really beautifully shows that skin exposure [to allergens] in early life can kind of skew the immune response,” said Kathryn Knoop, PhD, associate professor of immunology at the Mayo Clinic in Rochester, Minnesota. (Knoop was not involved in the study.) This early immune skewing could help explain why so many babies with eczema (40%) go on to develop asthma, allergies, or rhinitis — a link known as the atopic march.

Why eczema is so common in infancy has remained a persistent mystery, with studies hampered by ethics concerns surrounding infant skin biopsies. A fragile skin barrier is the most commonly accepted reason, but immunologist Yue Xing, PhD, who wanted to better understand her infant son’s mild eczema, was unconvinced.

Most studies have been conducted in mice — specifically, adult mice, Xing said. But what if baby mice (pups) were used as test subjects instead? 

“That was really an innovative thought,” said the study’s senior author, Shruti Naik, PhD, associate professor at Icahn School of Medicine at Mount Sinai in New York City. Xing is a postdoc in Naik’s lab and the lead author of the new study.

“We started looking at pups and how they respond,” Naik said. “This unblocked a completely new biology... It was [Xing’s] idea that we need to model it at the right age.”

How Early Life Shapes the Immune System

Tiny, fast-developing pup mice are difficult to study. Because their skin is thicker than a human’s, it has less of an inflammatory response. So Xing’s team bypassed the epidermis and introduced the allergic challenge directly to the pups’ immune cells.

She was surprised when it worked.

“As a scientist, I thought, ‘Oh, that’s awesome. We have a new phenotype, and we can dissect all the mechanisms,’” Xing said. “As a mom, I know I’m doing something that can really reflect what’s going on in babies compared to just explaining the prevalence of their sensitivity or their risk of allergic reactions.”

The findings build on a growing body of evidence about how the immune system — and its response to allergens — evolves in early life. Only recently have scientists started identifying mechanisms, like breast milk moderating what passes through the intestinal lining, or newly identified “thetis cells” suppressing inflammatory responses to food. Thetis cells work similarly to the dendritic cells that were the focus of this latest Nature paper, Knoop said.

Notably, the eczema mechanism contrasts with one of the most famous understandings of immune system priming — that small oral exposures to peanuts early in life can diminish peanut allergy risk. Some experts speculate that skin exposure affects tolerance differently from oral exposure.

“There’s a lot of thought in the field about if a baby potentially sees peanut butter through their skin first, or breathes in peanut particles and sees it in their lungs first, that they have an increased risk of peanut allergies, instead of just if they eat it first and see it through their intestines,” Knoop said.

What’s Next

Xing plans to explore a link she noticed with lung inflammation. “How does skin inflammation drive lung sensitivity to allergy?” she asked. “I want to figure this out with a more mechanistic study using my model.”

Knoop said the study raised many new questions, like whether bathing would help keep the skin barrier healthy by virtue of washing away potential allergens and what role key pathogens like Candida auris might play.

“When a baby has this open microbiota, potential pathobionts or pathogenic species can colonize really quickly,” Knoop said. “It’s important to understand what that microbiota looks like and how these pathogens might use those niches to drive these mechanisms.”