Transcriptional changes in dendritic cells underlying allergen specific induced tolerance in a mouse model

Sci Rep. 2022 Feb 18;12(1):2797. doi: 10.1038/s41598-022-06186-8.

Abstract

To investigate food allergy-tolerance mechanisms induced through allergen-specific immunotherapy we used RNA-Sequencing to measure gene expression in lymph-node-derived dendritic cells from Pru p 3-anaphylactic mice after immunotherapy with glycodendropeptides at 2 nM and 5 nM, leading to permanent tolerance and short-term desensitization, respectively. Gene expression was also measured in mice receiving no immunotherapy (anaphylaxis); and in which anaphylaxis could never occur (antigen-only). Compared to anaphylaxis, the antigen-only group showed the greatest number of expression-changes (411), followed by tolerant (186) and desensitized (119). Only 29 genes changed in all groups, including Il12b, Cebpb and Ifngr1. The desensitized group showed enrichment for genes related to chronic inflammatory response, secretory granule, and regulation of interleukin-12 production; the tolerant group showed genes related to cytokine receptor activity and glucocorticoid receptor binding, suggesting distinct pathways for similar outcomes. We identified genes and processes potentially involved in the restoration of long-term tolerance via allergen-specific immunotherapy, representing potential prognostic biomarkers.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Allergens / immunology
  • Allergens / pharmacology
  • Anaphylaxis / genetics
  • Anaphylaxis / immunology
  • Animals
  • Antigens, Plant / pharmacology
  • CCAAT-Enhancer-Binding Protein-beta / genetics*
  • Dendritic Cells / drug effects
  • Dendritic Cells / immunology
  • Desensitization, Immunologic*
  • Disease Models, Animal
  • Food Hypersensitivity / genetics
  • Food Hypersensitivity / immunology
  • Gene Expression Regulation / drug effects
  • Glycopeptides / pharmacology
  • Humans
  • Immune Tolerance / genetics*
  • Interferon gamma Receptor
  • Interleukin-12 / genetics
  • Interleukin-12 Subunit p40 / genetics*
  • Lymph Nodes / immunology
  • Mice
  • Plant Proteins / pharmacology
  • RNA-Seq
  • Receptors, Interferon / genetics*

Substances

  • Allergens
  • Antigens, Plant
  • CCAAT-Enhancer-Binding Protein-beta
  • Cebpb protein, mouse
  • Glycopeptides
  • Il12b protein, mouse
  • Interleukin-12 Subunit p40
  • Plant Proteins
  • Pru p 3 allergen
  • Receptors, Interferon
  • Interleukin-12