TNF-α-induced protein 3 is a key player in childhood asthma development and environment-mediated protection

Krusche, Johanna and Twardziok, Monika and Rehbach, Katharina and Böck, Andreas and Tsang, Miranda S. and Schröder, Paul C. and Kumbrink, Jörg and Kirchner, Thomas and Xing, Yuhan and Riedler, Josef and Dalphin, Jean-Charles and Pekkanen, Juha and Lauener, Roger and Roponen, Marjut and Li, Jing and Wong, Chun K. and Wong, Gary W. K. and Schaub, Bianca and Pasture study group, . (2019) TNF-α-induced protein 3 is a key player in childhood asthma development and environment-mediated protection. Journal of allergy and clinical immunology, 144 (6). pp. 1684-1696.e12.

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Official URL: https://edoc.unibas.ch/73473/

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Childhood asthma prevalence is significantly greater in urban areas compared with rural/farm environments. Murine studies have shown that TNF-α-induced protein 3 (TNFAIP3; A20), an anti-inflammatory regulator of nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) signaling, mediates environmentally induced asthma protection.; We aimed to determine the role of TNFAIP3 for asthma development in childhood and the immunomodulatory effects of environmental factors.; In a representative selection of 250 of 2168 children from 2 prospective birth cohorts and 2 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 Technologies) in isolated dendritic cells of schoolchildren and in cord blood mononuclear cells from newborns.; Anti-inflammatory TNFAIP3 gene and protein expression was consistently decreased, whereas proinflammatory Toll-like receptor 4 expression was increased in urban asthmatic patients (P < .05), reflecting their increased inflammatory status. Ex vivo farm dust or LPS stimulation restored TNFAIP3 expression to healthy levels in asthmatic patients and shifted NF-κB signaling-associated gene expression toward an anti-inflammatory state (P < .001). Farm/rural children had lower expression, indicating tolerance induction by continuous environmental exposure. Newborns with asthma at school age had reduced TNFAIP3 expression at birth, suggesting TNFAIP3 as a possible biomarker predicting subsequent asthma.; Our data indicate TNFAIP3 as a key regulator during childhood asthma development and its environmentally mediated protection. Because environmental dust exposure conferred the anti-inflammatory effects, it might represent a promising future agent for asthma prevention and treatment.
Faculties and Departments:09 Associated Institutions > Swiss Tropical and Public Health Institute (Swiss TPH)
09 Associated Institutions > Swiss Tropical and Public Health Institute (Swiss TPH) > Department of Epidemiology and Public Health (EPH) > Environmental Exposures and Health
UniBasel Contributors:Braun-Fahrländer, Charlotte
Item Type:Article, refereed
Article Subtype:Research Article
Note:Publication type according to Uni Basel Research Database: Journal article
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Last Modified:03 Mar 2020 13:52
Deposited On:03 Mar 2020 13:52

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