# Paneth Cell Secreted Effectors in Mucosal Innate Immunity

> **NIH NIH U01** · UNIVERSITY OF CALIFORNIA AT DAVIS · 2020 · $435,667

## Abstract

The immune system of mucosal tissues must effectively protect the host from pathogen invasion, while
facilitating homeostatic interactions with a diverse colonizing microbiota. A clear understanding of the key
molecules and mechanisms that achieve this delicate balance remains incomplete, leaving a gap in critical
knowledge. Paneth cells of the small intestine secrete large quantities of proteins and peptides into the lumen
that mediate both interrelated functions of host defense and maintenance of homeostasis. Compelling
published evidence from many laboratories, including ours, suggests that defective Paneth cell function
increases susceptibility to chronic inflammatory bowel disease (IBD) and to enteric pathogens. This
investigation will focus on a secreted protein that our preliminary data suggests is among the most abundant
secretory proteins of human Paneth cells, an understudied intestinal lectin named intelectin. Intelectin
orthologs widely span the animal Kingdom, from mammals to the invertebrate sea squirts. Recent published
data demonstrate that intelectin has molecular pattern binding activity characteristic of the innate immune
system, in that it binds to carbohydrates found on a variety microbes - through interaction with exocyclic 1, 2
diols - but does not bind to host carbohydrates because of steric hindrance. Our preliminary data identify
qualitative and quantitative aberrations of the two isoforms of intelectin (ITLN1 and ITLN2) in small intestinal
specimens from individuals with ileal Crohn's disease (CD) compared to controls. While statistically significant,
the mechanisms that may tie these changes to impaired innate immunity in CD are unknown and will be
investigated. Our hypothesis, based on published and preliminary data, is that intelectin is a critical mediator
of host-microbe interaction in the intestine. Aim 1 will determine the relative expression levels of ITLN1 and
ITLN2 in small intestinal CD and control specimens, and biochemically characterize intelectin isolated from
human small intestine. Aim 2 will investigate the in vitro activity of intelectin isoforms in vitro. Aim 3 will
establish innate immunological consequences of intelectin expression using newly generated C57BL/6 Itln-/-
mice. Our goal is to elucidate a fundamental understanding on the role of intelectin in mucosal protection, and
in so doing, fill a void in our understanding of a conserved, highly abundant secretory protein of human Paneth
cells. Successful completion of these studies will likely have broad impact on our mechanistic understanding
of innate immunity in the small intestine.

## Key facts

- **NIH application ID:** 9933796
- **Project number:** 5U01AI125956-05
- **Recipient organization:** UNIVERSITY OF CALIFORNIA AT DAVIS
- **Principal Investigator:** Charles L Bevins
- **Activity code:** U01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $435,667
- **Award type:** 5
- **Project period:** 2016-06-15 → 2022-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9933796

## Citation

> US National Institutes of Health, RePORTER application 9933796, Paneth Cell Secreted Effectors in Mucosal Innate Immunity (5U01AI125956-05). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/9933796. Licensed CC0.

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