# Mechanisms of Th17 and Treg cell dysregulation in oral mucosal inflammation during HIV disease

> **NIH NIH R01** · CASE WESTERN RESERVE UNIVERSITY · 2021 · $315,292

## Abstract

ABSTRACT
Residual oral inflammation along with chronic systemic immune activation is an important feature in many
(HIV)/Combined Antiretroviral therapy (cART) patients, and has been linked to a wide range of oral pathologies
including periodontitis, erythematous candidal lesions, viral infections and oral cancer. Although cART can
suppress plasma viral loads to undetectable levels, increased mortality is closely associated with mucosal
immune dysbiosis and persistent viral reservoirs in lymphoid tissues. To date, however, the majority of
research on immune activation has been derived from analysis of circulating quiescent T cells. How microbial
products from altered oral microbiome and opportunistic pathogens contribute to immune cell alterations and
oral mucosal dysbiosis is unknown. A better comprehension of this phenomenon, and various interactions
between immune cells, commensal and pathogenic microbes is needed to shed light on HIV-mediated immune
oral immune dysfunction. Our proposal will investigate these interactions with a specific focus on Th17 cells
and Tregs, the critical subsets of CD4+ T lymphocytes that play crucial roles in maintaining the mucosal barrier
integrity and preventing inflammation respectively. We hypothesize that loss of oral Th17 cells and increase in
proportions of dysfunctional Tregs contribute to residual oral inflammation in HIV+ patients. We will determine
the functions of interventional IL-21 in restoring Th17 cells during HIV infection. We will also define the role of
TLR signaling and IL-6 in inducing Treg plasticity, generating dysfunctional Tregs and contributing to oral immune
pathogenesis of HIV+ individuals. These studies will contribute to new ways of thinking about oral inflammation
in HIV+ individuals, and aid in generating novel therapeutic strategies to manage HIV mediated chronic oral
dysbiosis.
 This multidisciplinary project supported by a robust procurement network for human tonsillar and oral
tissues from HIV+ individuals will enable an unprecedented insight into HIV dependent oral mucosal
inflammatory mechanisms, and is compatible with Trans-NIH FY-2016 funding priorities for HIV research that
states “Study the effect of the CD4+ T-cell pool heterogeneity in terms of differentiation .. lineage (Th1, Th2,
Th17, Treg, Tfh), anatomic location (blood versus lymphoid tissues versus mucosal tissues)”, as area of
research priority. Most importantly, by defining the immune plasticity mechanisms in Th17 cells and Tregs during
HIV+/SIV infection, the project fits well with the program objectives for RFA-DE-17-006.

## Key facts

- **NIH application ID:** 10085578
- **Project number:** 5R01DE026923-05
- **Recipient organization:** CASE WESTERN RESERVE UNIVERSITY
- **Principal Investigator:** Pushpa Pandiyan
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $315,292
- **Award type:** 5
- **Project period:** 2017-04-01 → 2022-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10085578

## Citation

> US National Institutes of Health, RePORTER application 10085578, Mechanisms of Th17 and Treg cell dysregulation in oral mucosal inflammation during HIV disease (5R01DE026923-05). Retrieved via AI Analytics 2026-05-21 from https://api.ai-analytics.org/grant/nih/10085578. Licensed CC0.

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