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. 2018 Jan;141(1):382-390.e7.
doi: 10.1016/j.jaci.2017.04.051. Epub 2017 Jun 17.

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

Remo Frei  1 , Ruth Ferstl  2 , Caroline Roduit  3 , Mario Ziegler  2 , Elisa Schiavi  2 , Weronika Barcik  2 , Noelia Rodriguez-Perez  2 , Oliver F Wirz  2 , Marcin Wawrzyniak  2 , Benoit Pugin  2 , Dirk Nehrbass  4 , Marek Jutel  5 , Sylwia Smolinska  5 , Patrycja Konieczna  2 , Christian Bieli  3 , Susanne Loeliger  3 , Marco Waser  6 , Göran Pershagen  7 , Josef Riedler  8 , Martin Depner  9 , Bianca Schaub  9 , Jon Genuneit  10 , Harald Renz  11 , Juha Pekkanen  12 , Anne M Karvonen  13 , Jean-Charles Dalphin  14 , Marianne van Hage  15 , Gert Doekes  16 , Mübeccel Akdis  2 , Charlotte Braun-Fahrländer  6 , Cezmi A Akdis  2 , Erika von Mutius  17 , Liam O'Mahony  2 , Roger P Lauener  18 ; Prevention of Allergy Risk factors for Sensitization in Children Related to Farming and Anthroposophic Lifestyle (PARSIFAL) study group; Protection Against Allergy Study in Rural Environments (PASTURE)/Mechanisms of Early Protective Exposures on Allergy Development (EFRAIM) study group
Collaborators, Affiliations
Free article

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

Remo Frei et al. J Allergy Clin Immunol. 2018 Jan.
Free article

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.

Keywords: Farmers' children; N-glycolylneuraminic acid; airway inflammation; anti-inflammatory; colitis; nonmicrobial.

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