# Genome-targeted IL-23 receptor reporter rats for studying HLA-B27-dependent spondyloarthritis

> **NIH NIH R21** · UT SOUTHWESTERN MEDICAL CENTER · 2020 · $178,200

## Abstract

Ankylosing spondylitis (AS) is a polygenic inflammatory disorder of the spine and extremities
with potential for lifelong suffering. The histocompatibility allele HLA-B27 (B27) confers an odds
ratio of 50 for susceptibility to AS and accounts for about 20% of the genetic risk. The cytokine
pathway characterized by IL-17 has been shown to be central to the pathogenesis of AS and
many other chronic inflammatory conditions. IL-23 is a key cytokine that drives chronic
inflammation, and cells that produce IL-17 and cause chronic inflammation express receptors
for IL-23 (IL23R+ cells). There are several different classes of such cells, but it is not known
which one(s) are important in causing AS. Studies in mice genetically manipulated so that
IL23R+ cells can be conveniently detected in vivo or in vitro by fluorescence have been
extremely useful in characterizing the IL-23/IL-17 pathway in many different experimental
disease systems. There is no good mouse model for AS. However, rats transgenic for HLA-B27
and human β2-microglobulin (B27/ hβ2m TG rats) develop an AS-like disease
(spondyloarthritis), and this rat disease has been shown to be dependent upon IL-17 and to
share a number of other features with human AS. In this Exploratory/Developmental Research
Proposal, we plan to produce a genetically manipulated rat line in which cells expressing the IL-
23 receptor contain a fluorescent marker. Once the correct functioning of the fluorescent IL23R
reporter is validated, we will then breed these rats with B27/ hβ2m TG rats. Offspring carrying
all three genes will be studied for development of spondyloarthritis. The fluorescent IL23R+
cells will be identified and isolated from lymphoid tissue and from the sites of pathology, and
they will be characterized by flow cytometry for their cell surface markers, by RNA methods for
their gene expression profiles, and by in vitro assays of their cytokine production. These studies
should provide new and accurate information regarding the specific cell types that mediate the
chronic inflammation of spondyloarthritis. This experimental system can then be used to
identify potential therapeutic targets, and the IL23R reporter rats can be made available for
studies of other disease processes. Our goal will be to continue with studies to determine the
specific molecular role of HLA-B27 in activating the IL23R+ cells, through which we hope to
finally identify the specific role of HLA-B27 in causing rheumatic disease.

## Key facts

- **NIH application ID:** 9881254
- **Project number:** 5R21AR075150-02
- **Recipient organization:** UT SOUTHWESTERN MEDICAL CENTER
- **Principal Investigator:** JOEL D TAUROG
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $178,200
- **Award type:** 5
- **Project period:** 2019-03-01 → 2021-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9881254

## Citation

> US National Institutes of Health, RePORTER application 9881254, Genome-targeted IL-23 receptor reporter rats for studying HLA-B27-dependent spondyloarthritis (5R21AR075150-02). Retrieved via AI Analytics 2026-05-29 from https://api.ai-analytics.org/grant/nih/9881254. Licensed CC0.

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