TNFAIP3 is a key player in childhood asthma development and environment-mediated protection Publication date: Available online 2 August 2019 Source: Journal of Allergy and Clinical Immunology Author(s): Johanna Krusche, Monika Twardziok, Katharina Rehbach, Andreas Böck, Miranda S. Tsang, Paul C. Schröder, Jörg Kumbrink, Thomas Kirchner, Yuhan Xing, Josef Riedler, Jean-Charles Dalphin, Juha Pekkanen, Roger Lauener, Marjut Roponen, Jing Li, Chun K. Wong, Gary W.K. Wong, Bianca Schaub, PASTURE study group, Markus Ege, Martin Depner 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<0.05), reflecting their elevated inflammatory status. Ex vivo farm dust or LPS-stimulation restored TNFAIP3 expression to healthy levels in asthmatics and shifted NF-κB signaling associated gene expression towards an anti-inflammatory state (p<0.001). Farm/rural children showed lower expression indicating tolerance induction by continuous environmental exposure. Newborns with asthma at school-age showed reduced TNFAIP3 expression at birth, suggesting TNFAIP3 as a possible biomarker predicting subsequent asthma. 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. Graphical abstract

Pruritus in allergy and immunology Publication date: August 2019 Source: Journal of Allergy and Clinical Immunology, Volume 144, Issue 2 Author(s):

Editorial Board Publication date: August 2019 Source: Journal of Allergy and Clinical Immunology, Volume 144, Issue 2 Author(s):

Table of Contents Publication date: August 2019 Source: Journal of Allergy and Clinical Immunology, Volume 144, Issue 2 Author(s):

Brief Overview of This Month's JACI Publication date: August 2019 Source: Journal of Allergy and Clinical Immunology, Volume 144, Issue 2 Author(s):

Cover 1 Publication date: August 2019 Source: Journal of Allergy and Clinical Immunology, Volume 144, Issue 2 Author(s):

Corrigenda Publication date: August 2019 Source: Journal of Allergy and Clinical Immunology, Volume 144, Issue 2 Author(s):

Corrigenda Publication date: August 2019 Source: Journal of Allergy and Clinical Immunology, Volume 144, Issue 2 Author(s):

Reply Publication date: August 2019 Source: Journal of Allergy and Clinical Immunology, Volume 144, Issue 2 Author(s): Toril Mørkve Knudsen, Faisal I. Rezwan, Cecilie Svanes, John W. Holloway

Grandmaternal smoking during pregnancy and asthma in grandchildren Publication date: August 2019 Source: Journal of Allergy and Clinical Immunology, Volume 144, Issue 2 Author(s): Lennart Bråbäck, David Olsson, Bertil Forsberg