# The Regulatory Role of PIRB in CD4+ Th17 Mediated Colitis

> **NIH NIH F31** · UNIVERSITY OF MICHIGAN AT ANN ARBOR · 2020 · $37,520

## Abstract

Abstract
Inflammatory Bowel Disease (IBD) is a progressive chronic relapsing and remitting disease that results from an
unrestrained inflammatory response to intestinal microbes in a genetically susceptible host. In particular, CD4+
Th17-driven inflammatory response is thought to be instrumental in the augmentation and exacerbation of the
pathogenesis of IBD. Previously we identified an important role for the inhibitory receptor, paired Ig-like receptor
B (PIRB) in regulation of the initial innate-immune phase of the GI inflammatory response and development of
the colitic phenotype. We showed that PIRB restrained innate-immune induced myeloid cell activation and pro-
inflammatory cytokine (IL-1β, IL-6 and TNFα) response and that loss of this negative regulatory mechanism led
to increased myeloid proinflammatory cytokine production and exacerbation of the colitis phenotype. The
contribution of PIRB to the CD4+ T cell-component of the inflammatory response and colitis has previously not
been explored. In preliminary experiments we revealed a role for PIRB in the regulation of CD4+ T-cell-dependent
colitis. Our data suggest an intrinsic role for PIRB in the regulation of CD4+ T cells and development of the T-cell
dependent colitic phenotype and suggests divergent immune regulatory function of inhibitory receptors in innate
versus adaptive immune inflammatory responses in the onset of the IBD phenotype. We hypothesize that PIRB
regulates CD4+ Th17 development and enhances the pathogenic T-cell immune response in IBD. To test
this hypothesis, we propose the following two specifics aims: 1) To define the requirement of PIRB on the CD4+
Th17-dependent colitis; 2) To determine the role of PIRB in CD4+ Th17 differentiation and function. With respect
to the expected outcomes, the studies proposed in Aim I are expected to demonstrate a requirement for PIRB
in the development and onset of CD4+ Th17-driven colitic phenotype and Aim II are expected to demonstrate
that PIRB is required for CD4+ Th17 differentiation and function. Our proposed studies will identify an important
role for PIRB regulation of Th17-mediated inflammatory responses and will reveal a divergent role for PIRB in
regulating innate and adaptive immune responses. The training plan will take advantage of the opportunities
present in the research plan to enhance the training of the applicant in experimental immunology, in vivo mouse
disease model systems and provide career development skills which are essential for an independent research
scientist. The sponsor and advisors have a strong track record in successful mentorship of graduate students
and have expertise in immunology, IBD, and inhibitory receptors that will assure successful completion of the
proposed studies and best preparing the applicant to becoming an independent scientific investigator.

## Key facts

- **NIH application ID:** 9991344
- **Project number:** 1F31DK125007-01
- **Recipient organization:** UNIVERSITY OF MICHIGAN AT ANN ARBOR
- **Principal Investigator:** Jazib Naseer Uddin
- **Activity code:** F31 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $37,520
- **Award type:** 1
- **Project period:** 2020-03-05 → 2023-03-04

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9991344

## Citation

> US National Institutes of Health, RePORTER application 9991344, The Regulatory Role of PIRB in CD4+ Th17 Mediated Colitis (1F31DK125007-01). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/9991344. Licensed CC0.

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