# Aryl hydrocarbon receptor regulation of T follicular helper cells

> **NIH NIH F31** · UNIVERSITY OF ROCHESTER · 2022 · $17,281

## Abstract

PROJECT SUMMARY
Environmental factors are key modulators of immune function. However, the mechanisms by which immune cells
sense environmental cues, and integrate them into specific immune responses are not well understood. The aryl
hydrocarbon receptor (AHR) is one means by which environmental signals regulate immune responses. The
AHR is a ligand-regulated transcription factor that binds structurally diverse molecules, including certain
pollutants, dietary factors, and chemicals from microorganisms. Epidemiological and animal studies demonstrate
that AHR-binding compounds alter adaptive immune responses, but the cellular components and governing
mechanisms are not fully defined. Changes to CD4+ T cell differentiation and function are among the most
consistently observed effects of exposure to ligands of the AHR. We recently discovered that AHR activation
alters the percentage and number of T follicular helper cells (Tfh cells) and limits the production of virus-specific
antibodies during infection. This is significant because Tfh cells are required for humoral (antibody-mediated)
immunity, and environmental exposure to AHR ligands dampens antibody responses. Yet, how the AHR
modulates Tfh cells is not known. The proposed studies will test the central hypothesis that the AHR in CD4+ T
cells affects Tfh cell differentiation and function. Tfh cell differentiation involves CD4+ T cell activation,
differentiation, proliferation, and survival. The AHR could affect these processes singly or in combination to alter
Tfh cell differentiation. Thus, in the first aim will we will use lineage-specific Ahr gene ablation, multi-parameter
flow cytometry, and enzyme linked immunosorbent assays to determine whether AHR activation alters Tfh cell
differentiation by affecting CD4+ T cell activation, proliferation, and/or apoptosis. Additionally, these studies will
determine whether changes to Tfh cell differentiation and function are solely due to AHR-driven changes in CD4+
T cells. The second aim will use single cell RNA-seq and ChIP-seq to evaluate AHR regulation of genes in CD4+
T cells that encode factors critical to Tfh cell differentiation. Given that humans exposed to AHR-binding
pollutants exhibit greater incidence and severity of infections, as well as reduced antibody responses to common
vaccines, these findings will fill key gaps in knowledge and provide necessary data for translational studies with
populations exposed to AHR binding chemicals in their environment.

## Key facts

- **NIH application ID:** 10480766
- **Project number:** 5F31ES032301-02
- **Recipient organization:** UNIVERSITY OF ROCHESTER
- **Principal Investigator:** Cassandra Houser
- **Activity code:** F31 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $17,281
- **Award type:** 5
- **Project period:** 2021-09-01 → 2022-09-15

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10480766

## Citation

> US National Institutes of Health, RePORTER application 10480766, Aryl hydrocarbon receptor regulation of T follicular helper cells (5F31ES032301-02). Retrieved via AI Analytics 2026-05-26 from https://api.ai-analytics.org/grant/nih/10480766. Licensed CC0.

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