Short-Chain Fatty Acids Calibrate RARα Activity Regulating Food Sensitization

Front Immunol. 2021 Oct 14:12:737658. doi: 10.3389/fimmu.2021.737658. eCollection 2021.

Abstract

Gut-microbiota dysbiosis links to allergic diseases. The mechanism of the exacerbation of food allergy caused by gut-microbiota dysbiosis remains unknown. Regulation of retinoic acid receptor alpha (RARα) signaling is critical for gut immune homeostasis. Here we clarified that RARα in dendritic cells (DCs) promotes Th2 cell differentiation. Antibiotics treatment stimulates retinoic acid signaling in mucosal DCs. We found microbiota metabolites short-chain fatty acids (SCFAs) maintain IGF-1 levels in serum and mesenteric lymph nodes. The IGF-1/Akt pathway is essential for regulating the transcription of genes targeted by RARα. And RARα in DCs affects type I interferon (IFN-I) responses through regulating transcription of IFN-α. Our study identifies SCFAs crosstalk with RARα in dendritic cells as a critical modulator that plays a core role in promoting Th2 cells differentiation at a state of modified/disturbed microbiome.

Keywords: allergy; dendritic cell (DC); microbiota; short-chain fatty acids (SCFAs); type I interferon (IFN-I).

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Anti-Bacterial Agents / pharmacology
  • Bacteria / drug effects
  • Bacteria / metabolism*
  • Cells, Cultured
  • Dendritic Cells / drug effects
  • Dendritic Cells / immunology
  • Dendritic Cells / metabolism*
  • Disease Models, Animal
  • Dysbiosis
  • Fatty Acids, Volatile / metabolism*
  • Fatty Acids, Volatile / pharmacology
  • Food Hypersensitivity / genetics
  • Food Hypersensitivity / immunology
  • Food Hypersensitivity / metabolism*
  • Food Hypersensitivity / microbiology
  • Gastrointestinal Microbiome* / drug effects
  • Insulin-Like Growth Factor I / metabolism
  • Interferon Type I / metabolism
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Proto-Oncogene Proteins c-akt / metabolism
  • Retinoic Acid Receptor alpha / genetics
  • Retinoic Acid Receptor alpha / metabolism*
  • Signal Transduction
  • Th2 Cells / immunology
  • Th2 Cells / metabolism
  • Tretinoin / metabolism*

Substances

  • Anti-Bacterial Agents
  • Fatty Acids, Volatile
  • Interferon Type I
  • Rara protein, mouse
  • Retinoic Acid Receptor alpha
  • insulin-like growth factor-1, mouse
  • Tretinoin
  • Insulin-Like Growth Factor I
  • Proto-Oncogene Proteins c-akt