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. 2014 Jun;20(6):642-7.
doi: 10.1038/nm.3568. Epub 2014 May 11.

Lung microbiota promotes tolerance to allergens in neonates via PD-L1

Eva S Gollwitzer  1 , Sejal Saglani  2 , Aurélien Trompette  1 , Koshika Yadava  1 , Rebekah Sherburn  2 , Kathy D McCoy  3 , Laurent P Nicod  1 , Clare M Lloyd  2 , Benjamin J Marsland  1
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Lung microbiota promotes tolerance to allergens in neonates via PD-L1

Eva S Gollwitzer et al. Nat Med. 2014 Jun.

Abstract

Epidemiological data point toward a critical period in early life during which environmental cues can set an individual on a trajectory toward respiratory health or disease. The neonatal immune system matures during this period, although little is known about the signals that lead to its maturation. Here we report that the formation of the lung microbiota is a key parameter in this process. Immediately following birth, neonatal mice were prone to develop exaggerated airway eosinophilia, release type 2 helper T cell cytokines and exhibit airway hyper-responsiveness following exposure to house dust mite allergens, even though their lungs harbored high numbers of natural CD4(+)Foxp3(+)CD25(+)Helios(+) regulatory T (Treg) cells. During the first 2 weeks after birth, the bacterial load in the lungs increased, and representation of the bacterial phyla shifts from a predominance of Gammaproteobacteria and Firmicutes towards Bacteroidetes. The changes in the microbiota were associated with decreased aeroallergen responsiveness and the emergence of a Helios(-) Treg cell subset that required interaction with programmed death ligand 1 (PD-L1) for development. Absence of microbial colonization(10) or blockade of PD-L1 during the first 2 weeks postpartum maintained exaggerated responsiveness to allergens through to adulthood. Adoptive transfer of Treg cells from adult mice to neonates before aeroallergen exposure ameliorated disease. Thus, formation of the airway microbiota induces regulatory cells early in life, which, when dysregulated, can lead to sustained susceptibility to allergic airway inflammation in adulthood.

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References

    1. Immunity. 2011 May 27;34(5):794-806 - PubMed
    1. Nat Rev Immunol. 2010 Dec;10(12):861-8 - PubMed
    1. Nat Med. 2014 Feb;20(2):159-66 - PubMed
    1. Expert Rev Anti Infect Ther. 2011 Sep;9(9):731-45 - PubMed
    1. Immunol Allergy Clin North Am. 2008 Aug;28(3):631-47, ix-x - PubMed

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