# Regulation of TLR signaling in anti-commensal B cell responses and mucosal inflammation

> **NIH NIH R21** · BENAROYA RESEARCH INST AT VIRGINIA MASON · 2024 · $216,625

## Abstract

Project Summary
Mucosal surfaces house numerous commensal and symbiotic bacteria, viruses and other microorganisms, which
establish mutually beneficial interactions with their host. This microbial colonization relies on complex
interactions with the innate and adaptive immune systems, including the generation of antibodies against
commensal bacteria antigens. There is a pressing need to understand how adaptive immune responses to
commensals are regulated, and how failure of these mechanisms lead to inflammation and immune pathology.
Recent studies have identified a requirement for toll-like receptor (TLR) signaling in B cells in generating anti-
commensal antibodies. We have previously shown that the cell surface receptor integrin αvβ3 and components
of the autophagy pathway regulate TLR signaling in B cells to prevent overexpansion of autoreactive cells and
autoimmunity. In preliminary studies, we have shown that B cell-specific αv-knockout mice (αv-CD19 mice) have
increase numbers of spontaneous germinal centers in the intestine and are more susceptible to inflammatory
colitis. Based on these data, we hypothesize that αvβ3 regulates B cell responses to commensal bacteria to
maintain defense against infection but prevent overactive inflammatory responses. In this application we propose
to test this hypothesis by: (1) measuring anti-commensal antibodies and repertoires in αv-CD19 and control
mice, and following B cell responses after bacterial colonization; (2) determining the mechanism of increased
susceptibility to DSS colitis in αv-CD19 mice. This research is highly significant as it will provide important insights
into mechanisms of regulation of anti-commensal antibody responses, and if successful, will establish a new
paradigm linking dysregulated TLR signaling in B cells to susceptibility to colitis.

## Key facts

- **NIH application ID:** 10830429
- **Project number:** 5R21AI171921-02
- **Recipient organization:** BENAROYA RESEARCH INST AT VIRGINIA MASON
- **Principal Investigator:** Oliver James Harrison
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $216,625
- **Award type:** 5
- **Project period:** 2023-04-19 → 2025-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10830429

## Citation

> US National Institutes of Health, RePORTER application 10830429, Regulation of TLR signaling in anti-commensal B cell responses and mucosal inflammation (5R21AI171921-02). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10830429. Licensed CC0.

---

*[NIH grants dataset](/datasets/nih-grants) · CC0 1.0*