# GPR120 regulation of intestinal IgA responses and gut IgA-coated bacteria

> **NIH NIH R21** · UNIVERSITY OF TEXAS MED BR GALVESTON · 2021 · $197,500

## Abstract

Abstract
Increasing evidence suggests that the interactions between diet and the gut microbiota may play a critical role
in promoting or alleviating intestinal inflammation. However, little is known about the mechanisms involved. Free
fatty acids provide important energy sources as dietary nutrients, and act as signaling molecules in various
cellular processes. Most notable among the free fatty acids targets are mammalian G protein-coupled receptors
(GPR). GPR120 (also known as free fatty acid receptor 4, FFAR4) has been identified as a bona fide receptor
for long-chain fatty acids (LCFA) from dietary products and has a critical role in various physiological homeostasis
mechanisms such as adipogenesis. Its agonists are suggested as therapeutic targets for diabetes, metabolic
disorders, and inflammatory diseases. However, the mechanisms involved are still largely unknown. Intestinal
mucosal surfaces are protected by a first-line defense mediated by secretory Immunoglobulin A (SIgA), which
has been shown to be critical in mucosal immune defense. Intestinal IgA can be produced by both T cell-
dependent and T cell-independent pathways, however, the relative importance of each and how they are
regulated are still largely unclear. Although both are enriched in the intestines, there is a significant knowledge
gap regarding how LCFA regulate intestinal IgA responses as well as the role of the LCFA-IgA axis in the
regulation of host responses to microbiota and intestinal homeostasis. In this application, we will test the
hypothesis that GPR120 promotes intestinal IgA responses to microbiota through either substituting for TGFβ,
which is a critical cytokine in induction of B cell production of IgA, or through promoting TGFβ production by B
cells to enhance IgA production, leading to the preservation of intestinal immune homeostasis by regulating the
function and composition of gut microbiota. Aim 1 will define the molecular mechanisms by which GPR120
promotes intestinal IgA responses, and Aim 2 will determine whether GPR120-mediated intestinal production of
IgA alters gut microbiota to contribute to intestinal homeostasis. If successful, this project will potentially provide
a novel therapeutic target for treatment of patients with inflammatory bowel disease.

## Key facts

- **NIH application ID:** 10176396
- **Project number:** 5R21AI150210-02
- **Recipient organization:** UNIVERSITY OF TEXAS MED BR GALVESTON
- **Principal Investigator:** JIAREN SUN
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $197,500
- **Award type:** 5
- **Project period:** 2020-06-01 → 2024-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10176396

## Citation

> US National Institutes of Health, RePORTER application 10176396, GPR120 regulation of intestinal IgA responses and gut IgA-coated bacteria (5R21AI150210-02). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10176396. Licensed CC0.

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