# Back to Basics:  T Cellular Control of Nod2 in Uveitis

> **NIH NIH R01** · OREGON HEALTH & SCIENCE UNIVERSITY · 2020 · $315,000

## Abstract

PROJECT SUMMARY:
Uveitis is a complex set of diseases that together constitute ~15% of visual morbidity worldwide. For many
patients, uveitis can be a chronic life-long disease for which therapies may manage painful inflammation, but
do not provide a cure. For some with rheumatologic conditions, uveitis is also accompanied by diseases of the
joint, skin, or gut. Thus there is an urgent, unmet need to define key mechanisms of uveitis because of its
significant associated personal, social, and economic burdens. Innate immunity, as the first line of defense
against microbial pathogens, is a response that must be tightly regulated to avoid excessive inflammation and
tissue destruction. Such regulation is especially important in the eye, where multiple factors and processes act
together to limit inflammation so as to preserve the delicate cells and tissues critical to vision. The body senses
potentially pathogenic microbes in the environment via innate immune receptors, which are classified into
distinct families such as Toll-like receptors (TLRs) or NOD-like receptors (NLRs). One NLR, Nod2, not only
serves as an intracellular sensor of microbial and foreign motifs, but is causally linked to non-infectious
granulomatous uveitis in Blau syndrome. Using a model of T cell-mediated uveitis, experimental autoimmune
uveitis (EAU), an unexpected novel role was identified for Nod2 in protection against autoimmune uveitis. Such
protection was found to be conferred by CD4+ T cells and involved Nod2 modulation of the pathogenic capacity
of a subset of CD4+ T cells, Th17 cells, by controlling their production of the cytokine IL-17. Based on these
findings, as well as additional key preliminary data, this proposal aims to systematically probe the spectrum of
actions by which Nod2 could impact the evolution of disease-causing T cells responses. Using methodologies
that encompass molecular, cellular, and whole animal evaluation, experiments will test the central hypothesis
that Nod2 is a critical immunomodulator of autoreactive T cells that cause uveitis, and are organized in three
Specific Aims: 1) Delve into how Nod2 alters the uveitogenic potential of individual or populations of CD4+ T
cells; 2) Elucidate the effects of Nod2 on the internal operations of T cells that intersect with T-cell receptor
(TCR) signaling and T cell function; and 3) Determine whether Nod2 influences T cell development and
maturation of uveitogenic T cells. The role of Nod2 in autoimmune diseases is an area that has yet to be more
fully clarified. This research could potentially open up new avenues of investigation that could ultimately result
in novel strategies for therapeutic intervention of uveitis, as well as of other vision-threatening diseases.

## Key facts

- **NIH application ID:** 9857602
- **Project number:** 5R01EY025250-06
- **Recipient organization:** OREGON HEALTH & SCIENCE UNIVERSITY
- **Principal Investigator:** HOLLY Lallman ROSENZWEIG
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $315,000
- **Award type:** 5
- **Project period:** 2015-04-01 → 2024-02-29

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9857602

## Citation

> US National Institutes of Health, RePORTER application 9857602, Back to Basics:  T Cellular Control of Nod2 in Uveitis (5R01EY025250-06). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/9857602. Licensed CC0.

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