# IgA-Glycosylation: Mediator of Microbial Homeostasis and Intestinal Health?

> **NIH NIH R21** · YALE UNIVERSITY · 2020 · $209,375

## Abstract

Project Summary
Immunoglobulin A is the primary isotype secreted at mucosal surfaces and plays an important role in regulating
gut microbiota composition and enforcing host-microbiota symbiosis. The long-term goal of the proposed
research is to understand how IgA mediates these important effector functions, and to resolve the paradox of
how IgA targeting can support the growth of certain gut microbes, while restricting the growth of others. We will
explore the hypothesis that differential glycosylation of IgA can program unique antibody effector functions and
imbue this important secretory isotype with divergent effects on gut microbiota composition. Although the role
of glycosylation in regulating IgG function is now abundantly clear, almost nothing is known about how
glycosylation regulates the effector function of secretory IgA in the intestine, which exhibits even more complex
and extensive glycosylation patterns than IgG. Our proposal addresses this paradox by examining IgA
glycosylation patterns under a variety of inflammatory versus immunoregulatory conditions, and attempting to
connect changes in glycosylation to specific effects on microbial community structure. In Aim 1 we will examine
patterns of IgA glycosylation via lectin-based analyses, and through chromatography and mass-spectrometry.
We will compare IgA glycosylation in mice with a `healthy' microbial community, as well as mice with a
colitogenic `dysbiosis'; mice with and without T cells; and germ-free mice monocolonized with either Treg-
inducing or Th17-inducing bacterial species. In Aim 2 we will construct mice in which only B cells lack critical
glycosyltranferase enzymes to examine the effects of aberrant glycosylation of IgA on shaping of the microbial
community in the gut. The successful completion of these aims will result in the first full characterization of IgA
glycosylation in the gut, and may resolve an apparent paradox regarding the divergent effects of IgA coating on
colonization by and growth of specific gut microbes with inflammatory versus immunoregulatory capacities.
Understanding the role of glycosylation in IgA effector function is necessary to empower potential therapeutic
approaches that aim to use IgA to reshape microbial communities. Finally, these studies may lay the
foundation for a broader program exploring the role of secretory IgA glycosylation in human health and
disease.

## Key facts

- **NIH application ID:** 9850926
- **Project number:** 5R21AI137935-02
- **Recipient organization:** YALE UNIVERSITY
- **Principal Investigator:** NOAH WOLCOTT PALM
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $209,375
- **Award type:** 5
- **Project period:** 2019-01-16 → 2021-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9850926

## Citation

> US National Institutes of Health, RePORTER application 9850926, IgA-Glycosylation: Mediator of Microbial Homeostasis and Intestinal Health? (5R21AI137935-02). Retrieved via AI Analytics 2026-06-12 from https://api.ai-analytics.org/grant/nih/9850926. Licensed CC0.

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