Iron Deficiency Drives Th2-Mediated Immunity in Pediatric Atopic Dermatitis Through DNA Hypermethylation and TIGIT Suppression in IL-10-Producing Breg Cells

作者：Xiaofei Gao, Z. L. Hou, Xidie Li, Tingting Ouyang, Shuting Yu, Yuwei Wang, Ge Zhang, Yangyang Luo, Xieling He, Wei Liao, Wei Zhu · 发表于：Journal of Asthma and Allergy · 年份：2025 · DOI：10.2147/jaa.s544136 · 被引用次数：3 · 研究领域：Dermatology and Skin Diseases、Asthma and respiratory diseases、Allergic Rhinitis and Sensitization

Background: Pediatric atopic dermatitis (AD), a common chronic relapsing inflammatory skin disorder, often co-occurs with iron deficiency. However, the causal relationship and mechanisms linking iron homeostasis to AD pathogenesis remain unclear. This study investigates etiopathogenetic role of iron deficiency in childhood AD by analyzing molecular pathways and clinical impacts on disease progression. Methods: We have enrolled 298 pediatric AD patients based on the Hanifin and Rajka criteria to evaluate the relationship between peripheral iron and the severity of AD, as well as the levels of serum iron, ferritin, and transferrin in children with AD. The percentages of Th2 cells and IL-10-producing CD24 + CD38 + CD19 + regulatory B (Breg) cells were quantified by flow cytometry. RNA-sequencing and bioinformatic analysis were performed to explore the iron deficiency-sensitive genes in CD19 + B cells treated with Ciclopiroxolamine (CPX). The differentially expressed genes, including T cell immunoreceptor with immunoglobulin and tyrosine-based inhibitory motif (ITIM) domain ( TIGIT ) and IL10 , were further confirmed by RT-qPCR. 5-mC level was determined to evaluate the effect of iron deficiency on DNA methylation. TIGIT was inhibited in CD19 + B cells using a blocking antibody to assess its regulatory role in Breg cells. Results: Children with severe AD have lower levels of iron ions in peripheral blood compared with the mild patients ( P< 0.0001 ). Children with AD exhibited de...