TNFAIP3 is a key player in childhood asthma development and environment-mediated protection

Abstract Background Childhood asthma prevalence is significantly higher in urban areas compared to rural/farm environments. Murine studies have shown that TNFAIP3 (TNF-α-induced protein 3, A20), an anti-inflammatory regulator of NF-κB signaling, mediates environmental-induced asthma protection. Objective We aimed to determine the role of TNFAIP3 for asthma development in childhood and immune modulatory effects of environmental factors. Methods In a representative selection of 250 out of 2,168 children from two prospective birth cohort and two cross-sectional studies, we analyzed blood cells of healthy and asthmatic children from urban and rural/farm environments from Europe and China. PBMCs were stimulated ex vivo with dust from “asthma-protective” farms or LPS. NF-κB signaling-related gene and protein expression was assessed in PBMCs and multiplex gene expression assays (NanoString) in isolated dendritic cells of school-children and in CBMCs from newborns. Results Anti-inflammatory TNFAIP3 gene and protein expression was consistently decreased while pro-inflammatory TLR4 expression was increased in urban asthmatics (p Conclusion Our data indicate TNFAIP3 as key regulator during childhood asthma development and its environment-mediated protection. Since environmental dust exposure conferred anti-inflammatory effects, it may represent a promising future agent for asthma prevention and treatment.