# Control of Dendritic Cell Function by the Lipopolysaccharide (LPS)-Responsive and Beige-like Anchor protein (Lrba)

> **NIH NIH R03** · UT SOUTHWESTERN MEDICAL CENTER · 2020 · $122,563

## Abstract

Project Summary
LRBA protein deficiency is a monogenic cause of autoimmunity and inflammatory bowel disease (IBD) in
humans, but the basic cellular and molecular underpinnings responsible for the disease are not completely
understood. In an ongoing forward genetic screen for N-ethyl-N-nitrosourea (ENU)-induced mutations that
increase susceptibility to dextran sodium sulfate (DSS)-induced colitis in mice, we identified two nonsense
mutations in Lrba. We found that dendritic cells (DCs) contribute significantly to intestinal inflammation in Lrba-
deficient mice. In response to the stimulation of the Toll-like receptors (TLRs) TLR3, TLR7, and TLR9, Lrba-
/- DCs exhibited excessive chemokine and type I interferon production as well as exaggerated IRF3/7- and
PI3K/mTORC1-dependent signaling. Knockout of Unc93b1, a chaperone necessary for trafficking of TLR3,
TLR7, and TLR9 to endosomes, caused a significant amelioration of the cytokine expression and colitis
sensitivity after DSS treatment in Lrba-/- mice. Our data support a function for Lrba in restricting endosomal TLR
signaling and subsequent intestinal inflammation. We propose to further elucidate the role of Lrba in innate
immune cells in two interconnected and focused aims: Aim 1: To determine the role dendritic cell-intrinsic Lrba
plays in experimental colitis. Aim 2: Elucidate the cellular trafficking defects of Lrba-/- dendritic cells that lead to
exaggerated endosomal TLR responses. The aims in this proposal will help elucidate the mechanisms underlying
the role of dendritic cells in tissue inflammation and the coordination of immune signaling within them.

## Key facts

- **NIH application ID:** 10040959
- **Project number:** 1R03DK125631-01
- **Recipient organization:** UT SOUTHWESTERN MEDICAL CENTER
- **Principal Investigator:** Emre Erol Turer
- **Activity code:** R03 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $122,563
- **Award type:** 1
- **Project period:** 2020-07-10 → 2022-04-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10040959

## Citation

> US National Institutes of Health, RePORTER application 10040959, Control of Dendritic Cell Function by the Lipopolysaccharide (LPS)-Responsive and Beige-like Anchor protein (Lrba) (1R03DK125631-01). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10040959. Licensed CC0.

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