Exposure to nonmicrobial N-glycolylneuraminic acid protects farmers' children against airway inflammation and colitis

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Frei , R , Ferstl , R , Roduit , C , Ziegler , M , Schiavi , E , Barcik , W , Rodriguez-Perez , N , Wirz , O F , Wawrzyniak , M , Pugin , B , Nehrbass , D , Jutel , M , Smolinska , S , Konieczna , P , Bieli , C , Loeliger , S , Waser , M , Pershagen , G , Riedler , J , Depner , M , Schaub , B , Genuneit , J , Renz , H , Pekkanen , J , Karvonen , A M , Dalphin , J-C , van Hage , M , Doekes , G , Akdis , M , Braun-Fahrlander , C , Akdis , C A , von Mutius , E , O'Mahony , L , Lauener , R P , Prevention Allergy Risk Factors Se & Protection Against Allergy Study R 2018 , ' Exposure to nonmicrobial N-glycolylneuraminic acid protects farmers' children against airway inflammation and colitis ' , Journal of Allergy and Clinical Immunology , vol. 141 , no. 1 , pp. 382 - 390.e7 . https://doi.org/10.1016/j.jaci.2017.04.051

Title: Exposure to nonmicrobial N-glycolylneuraminic acid protects farmers' children against airway inflammation and colitis
Author: Frei, Remo; Ferstl, Ruth; Roduit, Caroline; Ziegler, Mario; Schiavi, Elisa; Barcik, Weronika; Rodriguez-Perez, Noelia; Wirz, Oliver F.; Wawrzyniak, Marcin; Pugin, Benoit; Nehrbass, Dirk; Jutel, Marek; Smolinska, Sylwia; Konieczna, Patrycja; Bieli, Christian; Loeliger, Susanne; Waser, Marco; Pershagen, Goeran; Riedler, Josef; Depner, Martin; Schaub, Bianca; Genuneit, Jon; Renz, Harald; Pekkanen, Juha; Karvonen, Anne M.; Dalphin, Jean-Charles; van Hage, Marianne; Doekes, Gert; Akdis, Mubeccel; Braun-Fahrlander, Charlotte; Akdis, Cezmi A.; von Mutius, Erika; O'Mahony, Liam; Lauener, Roger P.; Prevention Allergy Risk Factors Se; Protection Against Allergy Study R
Contributor organization: Department of Public Health
University of Helsinki
Date: 2018-01
Language: eng
Number of pages: 16
Belongs to series: Journal of Allergy and Clinical Immunology
ISSN: 0091-6749
DOI: https://doi.org/10.1016/j.jaci.2017.04.051
URI: http://hdl.handle.net/10138/231857
Abstract: Background: Childhood exposure to a farm environment has been shown to protect against the development of inflammatory diseases, such as allergy, asthma, and inflammatory bowel disease. Objective: We sought to investigate whether both exposure to microbes and exposure to structures of nonmicrobial origin, such as the sialic acid N-glycolylneuraminic acid (Neu5Gc), might play a significant role. Methods: Exposure to Neu5Gc was evaluated by quantifying anti-Neu5Gc antibody levels in sera of children enrolled in 2 farm studies: the Prevention of Allergy Risk factors for Sensitization in Children Related to Farming and Anthroposophic Lifestyle (PARSIFAL) study (n = 299) and the Protection Against Allergy Study in Rural Environments (PASTURE) birth cohort (cord blood [n = 836], 1 year [n = 734], 4.5 years [n = 700], and 6 years [n = 728]), and we associated them with asthma and wheeze. The effect of Neu5Gc was examined in murine airway inflammation and colitis models, and the role of Neu5Gc in regulating immune activation was assessed based on helper T-cell and regulatory T-cell activation in mice. Results: In children anti-Neu5Gc IgG levels correlated positively with living on a farm and increased peripheral blood forkhead box protein 3 expression and correlated inversely with wheezing and asthma in nonatopic subjects. Exposure to Neu5Gc in mice resulted in reduced airway hyperresponsiveness and inflammatory cell recruitment to the lung. Furthermore, Neu5Gc administration to mice reduced the severity of a colitis model. Mechanistically, we found that Neu5Gc exposure reduced IL-17(+) T-cell numbers and supported differentiation of regulatory T cells. Conclusions: In addition to microbial exposure, increased exposure to non microbial-derived Neu5Gc might contribute to the protective effects associated with the farm environment.
Subject: Farmers' children
N-glycolylneuraminic acid
airway inflammation
3121 General medicine, internal medicine and other clinical medicine
3142 Public health care science, environmental and occupational health
Peer reviewed: Yes
Rights: cc_by_nc_nd
Usage restriction: openAccess
Self-archived version: publishedVersion

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