# Molecular Mechanisms of IL-17-dependent autoimmune signaling

> **NIH NIH R01** · UNIVERSITY OF PITTSBURGH AT PITTSBURGH · 2021 · $518,902

## Abstract

IL-17 and Th17 cells drive pathology in a variety of autoimmune and pathologic
inflammatory conditions. Recently, biologic drugs targeting the IL-17 pathway have
shown clinical efficacy in psoriasis, and are under evaluation for other autoimmune and
inflammatory disease conditions. We have a long-standing interest in understanding the
fundamental basis for IL-17 signaling, with the premise that defining the molecular
mediators of disease pathology will ultimately help lead to development of the most
effective or specific therapeutic targets, diagnostics or biomarkers. IL-17 regulates
downstream inflammatory genes by transcriptional mechanisms, mainly involving the
canonical NF-κB pathway as well as CCAAT/Enhancer binding proteins (C/EBPs). IL-17
also activates numerous post-transcriptional mechanisms that control mRNA stability
and translation. In a screen to identify new intermediates involved in IL-17-dependent
downstream signaling, we discovered that IL-17 induces a novel RNA binding protein
(RBP) that was never previously linked to IL-17 signaling, T cells or autoimmune
pathology. Strikingly, cells lacking this RBP exhibited markedly impaired in IL-17
signaling, especially activation of NF-κB and C/EBPδ. In vivo, mice lacking this RBP
were refractory to IL-17-driven inflammatory diseases, including experimental
autoimmune encephalomyelitis (EAE), a model of MS, and AGN, a model of
autoimmune glomerulonephritis. The goals of this application are to define the
mechanisms by which this novel RBP pathway controls IL-17-dependent signal
transduction (Aim 1) and the tissue-specific consequences to IL-17-induced autoimmune
pathology using EAE as a model system (Aim 2).

## Key facts

- **NIH application ID:** 10065494
- **Project number:** 5R01AI147383-02
- **Recipient organization:** UNIVERSITY OF PITTSBURGH AT PITTSBURGH
- **Principal Investigator:** Sarah L Gaffen
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $518,902
- **Award type:** 5
- **Project period:** 2019-12-05 → 2024-11-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10065494

## Citation

> US National Institutes of Health, RePORTER application 10065494, Molecular Mechanisms of IL-17-dependent autoimmune signaling (5R01AI147383-02). Retrieved via AI Analytics 2026-06-11 from https://api.ai-analytics.org/grant/nih/10065494. Licensed CC0.

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