Urban kids and Allergies!

Recent research has identified a novel subset of T helper 2 (Th2) cells, termed Th2B cells, which may play a pivotal role in the development of allergic diseases and help explain the higher prevalence of allergies among urban children compared to their rural counterparts. This discovery, published in the journal Allergy, was led by researchers from the University of Rochester Medical Centre (URMC).

The study analysed blood samples from infants in urban settings and from the Old Order Mennonite (OOM) community in New York's Finger Lakes region, a rural population known for low allergy rates. Using advanced techniques like full-spectrum flow cytometry and single-cell RNA sequencing, researchers identified a unique effector memory Th2 cell population characterized by markers such as CD25⁺, CD127⁺, CD49d⁺, CCR4⁺, and CRTH2⁺, but lacking CD161 expression. These Th2B cells were elevated in urban infants, particularly those who later developed atopic dermatitis or food allergies, suggesting a potential role in allergic disease pathogenesis.¹

In contrast, OOM infants exhibited higher levels of regulatory T cells (Tregs), which are crucial for maintaining immune tolerance and preventing excessive inflammatory responses. This aligns with the "hygiene hypothesis," which posits that early-life exposure to diverse microbes, common in rural environments, supports the development of a balanced immune system less prone to allergic reactions.²

The researchers speculate that differences in gut microbiota development between urban and rural infants may influence the prevalence of Th2B cells. Urban environments, with reduced microbial diversity, may promote the emergence of pro-allergic immune cells, whereas rural settings rich in microbial exposure support immune tolerance.²

This study is part of a broader investigation into how early-life environmental exposures affect immune development. In 2023, Paediatric Allergy and Immunology team at UR Medicine Golisano Children’s Hospital received a $7 million grant to further explore environmental, microbiome, and immune differences between urban and rural infants. The goal is to identify protective factors that could inform preventive therapies, such as probiotics or microbiome-supporting interventions.

The identification of Th2B cells as a potential biomarker for allergy risk underscores the importance of early-life environmental exposures in shaping immune responses. Understanding these mechanisms may lead to targeted strategies to prevent allergic diseases, particularly in urban populations where allergy rates are rising.

References:

1. Catherine R. Pizzarello et al, A Phenotypically Distinct Human Th2 Cell Subpopulation Is Associated With Development of Allergic Disorders in Infancy, Allergy (2025). DOI: 10.1111/all.16489
   
   
2. Yang Z, Chen Z, Lin X, Yao S, Xian M, Ning X, Fu W, Jiang M, Li N, Xiao X, Feng M, Lian Z, Yang W, Ren X, Zheng Z, Zhao J, Wei N, Lu W, Roponen M, Schaub B, Wong GWK, Su Z, Wang C, Li J. Rural environment reduces allergic inflammation by modulating the gut microbiota. Gut Microbes. 2022 Jan-Dec;14(1):2125733. doi: 10.1080/19490976.2022.2125733. PMID: 36193874; PMCID: PMC9542937.