# Amphiregulin-Immunometabolism axis in oral immunity and inflammation during HIV infection

> **NIH NIH R01** · CASE WESTERN RESERVE UNIVERSITY · 2022 · $685,242

## Abstract

ABSTRACT
 Systemic inflammation and mortality in people living with HIV (PLWH) are associated with mucosal
immune dysfunction and persistent viral reservoirs in the mucosa and lymphoid tissues. In the previous
project period, we have demonstrated the role of CD4+ FOXP3+regulatory T cells (Treg) dysregulation in
contributing to aging- and HIV-associated oral inflammation. The dysfunctional Tregs that we uncovered in the
oral mucosa of PLWH mimic tissue-resident CD4+ T cells expressing high levels of PD-1 and amphiregulin
(AREG). These cells correlate with CD38+HLADR+ CD4+T cell hyperactivation and dysfunction, toll-like
receptor 2 (TLR-2), and inflammasome/IL-1β signaling in vivo, and require IL-1β/AKT pathways for their
expansion in the context of HIV infection. Here we propose to address the role of oral fungal dysbiosis in
establishing the inflammatory environment and triggering oral immune cells to become dysfunctional. Building
on our more recent results from salivary metabolome analysis in PLWH, we will examine the underlying
pathways at the interface of dectin-1, AREG, inflammasome, and immunometabolism signaling pathways in
three well-connected aims. Thus, our proposal will reveal new directions to manage oral immune-dysfunction
and thereby systemic inflammation, and alter current clinical practice.

## Key facts

- **NIH application ID:** 10480271
- **Project number:** 2R01DE026923-06A1
- **Recipient organization:** CASE WESTERN RESERVE UNIVERSITY
- **Principal Investigator:** Pushpa Pandiyan
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $685,242
- **Award type:** 2
- **Project period:** 2022-06-01 → 2027-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10480271

## Citation

> US National Institutes of Health, RePORTER application 10480271, Amphiregulin-Immunometabolism axis in oral immunity and inflammation during HIV infection (2R01DE026923-06A1). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10480271. Licensed CC0.

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