# IL-17 regulation of type-1 immunity in chronic viral infection

> **NIH NIH R01** · CORNELL UNIVERSITY · 2024 · $13,549

## Abstract

ABSTRACT
Viruses that successfully evade clearance without killing the host establish chronic infection.
However, unresolved low-grade inflammation causes morbidity over time, including development
of cancers. How to appropriately modulate immune responses to chronic infection without further
damaging the host represents a major clinical challenge. Type-17 immunity is invoked by
extracellular bacteria and fungi to control resident microbiota and invading pathogens at barrier
surfaces, and to promote tissue repair. Th17 cells have received much attention as drivers of
inflammation in chronic autoimmune diseases. However, there are sparse data regarding the role
of type-17 responses in response to viral infection. Here we have employed the well-characterized
model infection, LCMV clone 13, to test the role of IL-17 during chronic viral infection. IL-17 was
increased systemically during the switch to the chronic phase of infection. Using genetic and
antibody-mediated blockade of IL-17, our data unexpectedly reveal that IL-17 regulates Th1 and
CD8+ T cell activation, exhaustion and immunopathology during LCMV infection. We have
identified lymphoid stromal cells known as fibroblastic reticular cells (FRC) as key intermediaries
of IL-17 effects in secondary lymphoid tissues. Gene expression analysis and antibody-mediated
blockade support a role for excess IFNg in driving T cell exhaustion and immunopathology. These
unexpected findings lead to our central hypothesis that IL-17 has an immunoregulatory role during
chronic infection by limiting antiviral T cell IFNg-mediated exhaustion and immunopathology. This
project is designed to dissect the key elements that we have identified to be required in this
unexplored immunoregulatory pathway in chronic infection by probing the source of critical IL-17
(aim 1), LN stromal cells as targets of IL-17 (aim 2) and IFNg-mediated effects on exhaustion and
immunopathology in absence of IL-17 signaling (aim 3). Together these data will define a novel
and previously unexplored axis operating through IL-17 signaling in stromal cells to regulate IFNg-
mediated pathology, revealing new opportunities for future therapeutic intervention in chronically
infected people.

## Key facts

- **NIH application ID:** 11048664
- **Project number:** 3R01AI170773-03S1
- **Recipient organization:** CORNELL UNIVERSITY
- **Principal Investigator:** Mandy J McGeachy
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $13,549
- **Award type:** 3
- **Project period:** 2022-06-10 → 2027-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/11048664

## Citation

> US National Institutes of Health, RePORTER application 11048664, IL-17 regulation of type-1 immunity in chronic viral infection (3R01AI170773-03S1). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/11048664. Licensed CC0.

---

*[NIH grants dataset](/datasets/nih-grants) · CC0 1.0*