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

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Date
2017
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 Göran
Riedler Josef
Depner Martin et al (incl. Roponen Marjut
Hirvonen Marja-Riitta
Pekkanen Juha)
Unique identifier
10.1016/j.jaci.2017.04.051
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Citation
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 Göran. Riedler Josef. Depner Martin et al (incl. Roponen Marjut. Hirvonen Marja-Riitta. Pekkanen Juha). (2017). Exposure to nonmicrobial N-glycolylneuraminic acid protects farmers' children against airway inflammation and colitis.  JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY, 141 (1) , 382-390. 10.1016/j.jaci.2017.04.051.
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© Authors
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CC BY-NC-ND https://creativecommons.org/licenses/by-nc-nd/4.0/
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.

Subjects
Farmers' children   nonmicrobial   N-glycolylneuraminic acid   airway inflammation   colitis   anti-inflammatory   
URI
https://erepo.uef.fi/handle/123456789/6024
Link to the original item
http://dx.doi.org/10.1016/j.jaci.2017.04.051
Publisher
Elsevier BV
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  • Luonnontieteiden ja metsätieteiden tiedekunta
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