# The IL-23/IL-17 Axis in Inflammatory Arthritis

> **NIH NIH R01** · UNIVERSITY OF CALIFORNIA AT DAVIS · 2020 · $22,052

## Abstract

PROJECT SUMMARY/ABSTRACT
About 50 million Americans (22%) suffer from some form of inflammatory arthritis and estimates are that, with
the aging population worldwide, 67 million adults will have arthritis by 2030 with an economic impact higher
than $128 billion dollars. Although interleukin-23 (IL-23) has been implicated in the pathogenesis of arthritis,
the molecular mechanisms remain unknown. Since the discovery of IL-23 regulation of pathogenic T helper
cells that express interleukin-17 (Th17) the importance of direct actions of IL-23 in arthritis is overshadowed.
To highlight its importance we developed gene-transfer models of IL-23 and IL-17A and using these models
we established that IL-23 is a potent inducer of arthritis, independently of IL-17A. Dissection of IL-23 from the
IL- 23/IL-17A axis has allowed us to uncover novel mechanisms of myeloid cell activation previously
overlooked. We identified that IL-23 induces arthritis independently of Th17 cells and through activation of
myeloid cells. T cells and myeloid cells share a requirement for costimulatory signals that are mediated by
ITAMs. The ITAM is a conserved signaling motif contained in the cytoplasmic domain of transmembrane
adaptor molecules that are associated and transmit signals from various immunoreceptors present in
haematopoietic progenitors. We have identified that IL-23 induces the activation and recruitment of MDL-1
receptor that orchestrates synovial and skin inflammation via the activation of osteoclasts and neutrophils
respectively. Discovering the cellular and molecular mechanisms that dictate recruitment and activation of
osteoclasts in inflammatory arthritis is central to preventing this disabling condition. Detailed understanding of
these cellular and molecular interactions will yield insights into regulation of arthritis that can be exploited for
therapeutic interventions.

## Key facts

- **NIH application ID:** 10110275
- **Project number:** 3R01AR062173-05A1S1
- **Recipient organization:** UNIVERSITY OF CALIFORNIA AT DAVIS
- **Principal Investigator:** Iannis Elias Adamopoulos
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $22,052
- **Award type:** 3
- **Project period:** 2020-03-01 → 2024-11-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10110275

## Citation

> US National Institutes of Health, RePORTER application 10110275, The IL-23/IL-17 Axis in Inflammatory Arthritis (3R01AR062173-05A1S1). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/10110275. Licensed CC0.

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