TY - JOUR
T1 - Antibiotics in neonatal life increase murine susceptibility to experimental psoriasis
AU - Zanvit, Peter
AU - Konkel, Joanne E.
AU - Jiao, Xue
AU - Kasagi, Shimpei
AU - Zhang, Dunfang
AU - Wu, Ruiqing
AU - Chia, Cheryl
AU - Ajami, Nadim J.
AU - Smith, Daniel P.
AU - Petrosino, Joseph F.
AU - Abbatiello, Brittany
AU - Nakatsukasa, Hiroko
AU - Chen, Qianming
AU - Belkaid, Yasmine
AU - Chen, Zi Jiang
AU - Chen, Wanjun
N1 - Funding Information:
We thank Nathan Goldberg at MIU, NIDCR for critical reading of the manuscript. We thank Ginger A. Metcalf, Donna M. Muzny, and Richard A. Gibbs at the Human Genome Sequencing Center at Baylor College of Medicine for their support in sequencing. The Intramural Research Program of the NIH, NIDCR, supported this research.
Publisher Copyright:
© 2015 Macmillan Publishers Limited. All rights reserved.
PY - 2015/9/29
Y1 - 2015/9/29
N2 - Psoriasis is an inflammatory skin disease affecting a 1/42% of the worlda € s population, but the aetiology remains incompletely understood. Recently, microbiota have been shown to differentially regulate the development of autoimmune diseases, but their influence on psoriasis is incompletely understood. We show here that adult mice treated with antibiotics that target Gram-negative and Gram-positive bacteria develop ameliorated psoriasiform dermatitis induced by imiquimod, with decreased pro-inflammatory IL-17- and IL-22-producing T cells. Surprisingly, mice treated neonatally with these antibiotics develop exacerbated psoriasis induced by imiquimod or recombinant IL-23 injection when challenged as adults, with increased IL-22-producing I 3I + T cells. 16S rRNA gene compositional analysis reveals that neonatal antibiotic-treatment dysregulates gut and skin microbiota in adults, which is associated with increased susceptibility to experimental psoriasis. This link between neonatal antibiotic-mediated imbalance in microbiota and development of experimental psoriasis provides precedence for further investigation of its specific aetiology as it relates to human psoriasis.
AB - Psoriasis is an inflammatory skin disease affecting a 1/42% of the worlda € s population, but the aetiology remains incompletely understood. Recently, microbiota have been shown to differentially regulate the development of autoimmune diseases, but their influence on psoriasis is incompletely understood. We show here that adult mice treated with antibiotics that target Gram-negative and Gram-positive bacteria develop ameliorated psoriasiform dermatitis induced by imiquimod, with decreased pro-inflammatory IL-17- and IL-22-producing T cells. Surprisingly, mice treated neonatally with these antibiotics develop exacerbated psoriasis induced by imiquimod or recombinant IL-23 injection when challenged as adults, with increased IL-22-producing I 3I + T cells. 16S rRNA gene compositional analysis reveals that neonatal antibiotic-treatment dysregulates gut and skin microbiota in adults, which is associated with increased susceptibility to experimental psoriasis. This link between neonatal antibiotic-mediated imbalance in microbiota and development of experimental psoriasis provides precedence for further investigation of its specific aetiology as it relates to human psoriasis.
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U2 - 10.1038/ncomms9424
DO - 10.1038/ncomms9424
M3 - Article
C2 - 26416167
AN - SCOPUS:84942770640
SN - 2041-1723
VL - 6
JO - Nature Communications
JF - Nature Communications
M1 - 8424
ER -
