1. Academic Validation
  2. The bile acid-activated retinoic acid response in dendritic cells is involved in food allergen sensitization

The bile acid-activated retinoic acid response in dendritic cells is involved in food allergen sensitization

  • Allergy. 2022 Feb;77(2):483-498. doi: 10.1111/all.15039.
Renlan Wu 1 2 Xiefang Yuan 1 Xingjie Li 1 3 Ning Ma 1 Hongyu Jiang 1 3 Hongmei Tang 1 Guofeng Xu 1 Zhigang Liu 4 Zongde Zhang 1 3 2
Affiliations

Affiliations

  • 1 Inflammation & Allergic Diseases Research Unit, Affiliated Hospital of Southwest Medical University, Sichuan, China.
  • 2 Model Animal Research Center, Nanjing University, Nanjing, China.
  • 3 The School of Basic Medical Sciences, Southwest Medical University, Sichuan, China.
  • 4 State Key Laboratory of Respiratory Disease for Allergy at, Shenzhen University, Shenzhen University School of Medicine, Shenzhen, China.
Abstract

Background: Alteration of commensal microbiota is highly correlated with the prevalence of allergic reactions to food in the gastrointestinal tract. The mechanisms by which microbiota modulate food allergen sensitization in the mucosal site are not fully understood.

Methods: We generate DCs specific knockout of retinoic acid receptor α (Rara) gene mice (DC KO Rara) to evaluate food sensitization. The bile acid-activated retinoic acid response was evaluated by flow cytometry, real-time RT-PCR and Illumina transcriptome Sequencing. The global effect of Abx treatment on BA profiles in the mucosal lymph tissue mLN in mice was examined by UPLC-MS analysis.

Results: In this study, we demonstrate that depletion of commensal gut bacteria leads to enhanced retinoic acid (RA) signaling in mucosal dendritic cells (DCs). RA signaling in DCs is required for the production of food allergen-specific IgE and IgG1. Antibiotics induced an enlarged bile acid (BA) pool, and dysregulated BA profiles contributed to enhanced RA signaling in mucosal DCs. BA-activated RA signaling promoted DC upregulation of interferon I signature, RA signature, OX40L, and PDL2, which may lead to T helper 2 differentiation of CD4+ T cells. BA-activated RA signaling involved the farnesoid X receptor and RA receptor α (RARa) interaction. Depletion of bile acid reduces food allergen specific IgE and IgG1 levels in mice.

Conclusion: Our research unveils a mechanism of food sensitization modulated by BA-RA signaling in DCs, which suggests a potential new approach for the intervention of food allergic reactions.

Keywords

animal models; basic immunology; basic mechanisms; dendritic cells; food allergy; immunoglobulin E; microbiome; mucosal immunity.

Figures
Products