Dietary protein shapes the profile and repertoire of intestinal CD4 + T cells.
Ainsley LockhartAubrey ReedTiago Rezende de CastroCalvin HermanMaria Cecilia Campos CanessoDaniel MucidaPublished in: bioRxiv : the preprint server for biology (2023)
The intestinal immune system must tolerate food antigens to avoid allergy, a process requiring CD4 + T cells. Combining antigenically defined diets with gnotobiotic models, we show that food and microbiota distinctly influence the profile and T cell receptor repertoire of intestinal CD4 + T cells. Independent of the microbiota, dietary proteins contributed to accumulation and clonal selection of antigen-experienced CD4 + T cells at the intestinal epithelium, imprinting a tissue specialized transcriptional program including cytotoxic genes on both conventional and regulatory CD4 + T cells (Tregs). This steady state CD4 + T cell response to food was disrupted by inflammatory challenge, and protection against food allergy in this context was associated with Treg clonal expansion and decreased pro-inflammatory gene expression. Finally, we identified both steady state epithelium-adapted CD4 + T cells and tolerance-induced Tregs that recognize dietary antigens, suggesting that both cell types may be critical for preventing inappropriate immune responses to food.
Keyphrases
- gene expression
- immune response
- human health
- dendritic cells
- transcription factor
- oxidative stress
- weight loss
- dna methylation
- single cell
- high glucose
- genome wide
- mesenchymal stem cells
- binding protein
- quality improvement
- small molecule
- risk assessment
- toll like receptor
- drug induced
- endothelial cells
- diabetic rats
- bone marrow
- functional connectivity
- heat stress