# Interaction of Galectin-9 and Pregnancy-Specific Glycoprotein 1 in the Regulation of Cells of the Innate and Adaptive Immune System

> **NIH NIH R21** · HENRY M. JACKSON FDN FOR THE ADV MIL/MED · 2022 · $228,744

## Abstract

ABSTRACT
The importance of placental and decidual secreted factors as mediators of the immunological
adjustments needed to accommodate the genetically different mother and fetus during
hemochorial pregnancies is well recognized. Galectins are a family of lectins with intracellular and
extracellular functions. Secreted galectins bind to N-acetyllactosamine (LacNAc) and form lattices
between glycoproteins on the surface of cells and between cells, promoting a plethora of
biological activities including regulation of the adaptive and innate immune response. Members
of the galectin family exhibit notable differences in carbohydrate specificity and affinity resulting
in different functions. Recently, Galectin-9 (Gal-9), which is expressed at the maternal fetal-
interface, has been suggested to play a role in maternal T-cell tolerance by binding to its receptors
which include among others T cell immunoglobulin and mucin-domain containing-3 (Tim-3) and
CD44. On the other hand, Gal-9 has been reported to induce the secretion of pro-inflammatory
cytokines by myeloid cells. Recently, we found that Pregnancy-specific glycoprotein 1(PSG1),
which is secreted by placental trophoblasts at increasing concentration as pregnancy progresses,
binds to Gal-9. PSG1 binds to Gal-9 with high affinity and the interaction is glycan-mediated.
Importantly, the concentration of PSG1 is lower than normal in some pregnancy complications
including pre-eclampsia.
 Activation of the innate immune system has been proposed to contribute to trophoblast
invasion in the early decidua and to parturition, however it is also associated with adverse
pregnancy outcomes when it occurs in the second and third trimesters. Therefore, the temporal
and spatial aspects of reducing inflammation during pregnancy represent a complex and essential
process for pregnancy success. We propose that the newly found interaction between Gal-9 and
PSG1 contributes to the qualitative differences in the immune response required for pregnancy
success and that besides their previously identified individual functions, the interplay between
these two proteins plays an important role in the modulation of immune cells. Therefore we
propose to carry out the following Specific Aims: (1) Analyze the binding of native and recombinant
PSG1 to the N-terminal and C-terminal carbohydrate recognition domains of Gal-9. (2) Determine
the individual and combined effects of PSG1 and Gal-9 or the individual Gal-9 CRDs on the
phenotype and secretion of cytokines by monocytes and decidual macrophages. (3) Determine
the effect of individual and combined treatment of PSG1 and Gal-9 in human CD4+ T-cell
apoptosis and frequency of CD4+ FoxP3+ T-regulatory cells.

## Key facts

- **NIH application ID:** 10434937
- **Project number:** 5R21AI156058-02
- **Recipient organization:** HENRY M. JACKSON FDN FOR THE ADV MIL/MED
- **Principal Investigator:** Gabriela S Dveksler
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $228,744
- **Award type:** 5
- **Project period:** 2021-06-18 → 2025-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10434937

## Citation

> US National Institutes of Health, RePORTER application 10434937, Interaction of Galectin-9 and Pregnancy-Specific Glycoprotein 1 in the Regulation of Cells of the Innate and Adaptive Immune System (5R21AI156058-02). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10434937. Licensed CC0.

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