Early-life immune system differences drive childhood eczema risk

A team of researchers at the Icahn School of Medicine at Mount Sinai, Weill Cornell Medicine, and other institutions have uncovered a key biological explanation for why eczema so often starts in childhood. The study, in young mice, found that some types of immune cells in early-life skin are more reactive than those in adults, a difference that may help explain why children are more vulnerable to inflammation and allergic skin disease.

The findings suggest that early childhood represents a critical window for immune-driven skin disease and may shed light on why eczema is often the first condition in a broader pattern of allergic disease. They were reported in the February 25 online issue of Nature [DOI: 10.1038/s41586-026-10162-x].

Eczema affects nearly one in four children and often appears early in life. It can also precede other allergic conditions, including asthma and food allergies. Until now, scientists have not fully understood why the disease is so strongly linked to early childhood.

We found that allergy risk is shaped very early in life, when the skin's immune system is biologically programmed to overreact to allergens, with important consequences for understanding how immune-mediated diseases emerge and should be treated. By pinpointing the cells and hormonal signals that control this window of vulnerability, we open the door to strategies that could prevent allergic disease before it spreads from the skin to the lungs, gut, and beyond."

Shruti Naik, PhD, senior study author, Associate Professor of Immunology and Immunotherapy, and Dermatology, Icahn School of Medicine

The researchers discovered that a specific immune cell type, the dendritic cell, in young skin behaves differently than in adults. These cells do not overreact to everything-but when it comes to allergens, they respond faster and more strongly, setting the stage for inflammation and eczema early in life. In adult skin, the same cells are far less reactive.

To understand why allergies often start in early childhood, researchers exposed infant mice to everyday allergens such as dust mites and mold. Unlike adult mice, the infants developed strong skin inflammation, revealing a brief early-life period when the skin's immune system is especially sensitive.

The scientists traced this response to dendritic cells, which are unusually active shortly after birth and triggers allergic inflammation. When this pathway was blocked, the young mice did not develop skin allergies.

The team also found that infants lack normal levels of stress hormones that later help keep immune reactions in check, allowing these allergic responses to take hold. Importantly, signs of the same immune activity were found in skin samples from children with early-onset eczema, but not in adults, suggesting this early-life window may also be important in humans.

"This work was only possible through a true clinic-to-lab collaboration-where insights from pediatric patients shaped the questions we asked in the lab," says study co-author Emma Guttman-Yassky, MD, PhD, the Waldman Professor of Dermatology and Immunology and Health System Chair of the Kimberly and Eric J. Waldman Department of Dermatology at the Icahn School of Medicine. "By studying allergic disease where it actually begins, in early life, and by modeling clinically relevant allergens and disease features, lead author Yue Xing, PhD, uncovered immune biology that simply doesn't appear in adult models. By revealing what's unique about the early-life immune system, this work explains why eczema so often begins in infancy."

Next, the investigators plan to explore ways to block this early-life immune pathway to stop allergic disease before it spreads from the skin to other organs. 

"Beyond eczema, this study reinforces a critical point for medicine," says Dr. Naik. "Children are not simply small adults when it comes to immunity. Their immune system follows a unique set of rules, and recognizing that difference is essential for understanding-and ultimately preventing-allergic, immune-driven diseases that begin in childhood."