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.
Highlights
Vitamin A plays a crucial role in maintaining homeostasis at the intestinal barrier and balancing immunity and tolerance
To assess whether gut bacteria have an effect on retinoic acid (RA) signaling, we established an animal model with gut microbiota dysbiosis by treating mice with a cocktail of antibiotics, and RA signaling reporter mice which harbored a RA response element (RARE) upstream of b-galactosidase (LacZ) were used
These results indicate that gut bacterial regulation of RA signaling was specific in intestinal dendritic cells
Summary
Vitamin A plays a crucial role in maintaining homeostasis at the intestinal barrier and balancing immunity and tolerance. As its principal active metabolite, retinoic acid (RA) implicates diverse inflammatory responses, which affect innate and adaptive immunity [1]. RA involved in immunological procession regulates gene expression through binding several families nuclear hormone receptor, including retinoic acid receptors (RARs) a, b, and g, retinoid X receptors (RXRs) a, b and g, and the peroxisome proliferator-activated receptors (PPARs) b, d [2]. The RAR family includes RARa, RARb, and RARg. Lack of RA associates with abnormal migration of immune cells to the intestine and impaired immune tolerance [3, 4]. Whether RARa in DCs regulates immune response, especially the T cell differentiation, is not clear
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