Year: 2025
Type: article
Abstract: Description One link between the environment and autoimmune disease is the aryl hydrocarbon receptor (AhR), a ligand activated transcription factor that can bind a diverse repertoire of ligands. In a variety of autoimmune disease mouse models, AhR activation has been linked to the induction of both proinflammatory T helper 17 cells (Th17) and regulatory T cells (Tregs). However, the factors that influence Th17 or Treg differentiation remain unclear. Using the non-obese diabetic (NOD) model for type 1 diabetes (T1D), studies in our laboratory have shown that the pharmacokinetics of AhR ligands and the location of AhR activation influences CD4+ T cell fates and the development of hyperglycemia. The overarching hypothesis is that the outcome of CD4+ T cell differentiation following exposure to AhR ligands is driven by interactions with the gut microbiome. To test this hypothesis, we analyzed CD4+ T cell differentiation in two different NOD mouse models: 1) AhR knockout (KO) specific pathogen free (SPF) mice and 2) gnotobiotic mice. We observed AhR KO mice had a delayed onset of hyperglycemia, an increase in intestinal Tregs when compared to AhR wildtype (WT) NOD mice under SPF conditions, and microbial changes in the gut. These AhR-mediated differences in Tregs and in the development of hyperglycemia are dependent on the gut microbiota, demonstrating AhR-microbe interactions in the gut influence CD4+ T cell differentiation outcomes. Funding Sources The project described was supported by NIDDK R00DK117509, NIEHS-funded UC Davis EHSC under P30 ES023513, and T32 ES007059 from NIH NIEHS. Topic Categories Lymphocyte Differentiation and Peripheral Maintenance (LYM)
Source: The Journal of Immunology
Authors: Clarisa Martinez, Keegan Malany, Michael Goodson, Allison Ehrlich
Institution: University of California, Davis
Language: English
Topic: T-cell and B-cell Immunology
Subfield: Immunology
Field: Immunology and Microbiology
Domain: Life Sciences
Open Access status: bronze
OpenAlex ID: W4416446376
FWCI:
Cites:
Cited by:
Related to: