Antibiotics in neonatal life increase murine susceptibility to experimental psoriasis

Nat Commun. 2015 Sep 29;6:8424. doi: 10.1038/ncomms9424.

Abstract

Psoriasis is an inflammatory skin disease affecting ∼2% of the world'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 γδ(+) 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.

Publication types

  • Research Support, N.I.H., Intramural

MeSH terms

  • Aminoquinolines
  • Animals
  • Animals, Newborn
  • Anti-Bacterial Agents / adverse effects*
  • Disease Susceptibility
  • Drug Interactions
  • Imiquimod
  • Interleukin-17 / metabolism
  • Interleukins / metabolism
  • Mice
  • Mice, Inbred C57BL
  • Microbiota / drug effects*
  • Polymyxin B / adverse effects*
  • Psoriasis / chemically induced*
  • Psoriasis / drug therapy
  • Psoriasis / metabolism
  • Skin / immunology
  • T-Lymphocytes / metabolism
  • Vancomycin / adverse effects*

Substances

  • Aminoquinolines
  • Anti-Bacterial Agents
  • Interleukin-17
  • Interleukins
  • Vancomycin
  • Polymyxin B
  • Imiquimod
  • interleukin-22