Anti-Inflammatory Effects of Polyglycerol Sulfates and Natural Polyanions in Type 2 Inflammation

TL;DR

This paper explores how polyglycerol sulfates and other natural polyanions can reduce type 2 inflammation, which is linked to chronic atopic diseases like asthma and eczema.

Contribution

The study identifies polyglycerol sulfates as inhibitors of TSLP and fibronectin, offering a novel anti-inflammatory strategy for type 2 immune responses.

Findings

Polyglycerol sulfates strongly bind to TSLP and fibronectin, inhibiting type 2 inflammation.

Adding polyglycerol sulfate to inflamed bronchial epithelium models reduced TSLP expression and interleukin 6 secretion.

These findings suggest potential therapeutic applications for managing atopic diseases.

Abstract

Type
2 inflammation is an essential defense mechanism
of the innate
and adaptive immune systems, but when dysregulated, it can cause chronic
atopic diseases like allergic asthma and atopic dermatitis. Thymic
stromal lymphopoietin (TSLP) helps drive type 2 inflammation by guiding
T cells toward a type 2 helper cell (TH2) subtype and stimulating
B cells’ antibody production. Fibronectin (FN) has recently
been found at elevated levels in the plasma of children with atopic
dermatitis and shown a potential proinflammatory role in bronchial
epithelium tissue models. Both proteins’ surface charges suggest
potential interaction with charged molecules. Seeking new strategies
against type 2 inflammation, we found that negatively charged polyglycerol
sulfates strongly bind to TSLP and FN. We confirmed that these molecules
inhibit inflammation by reducing the TSLP-mediated type 2 polarization
of CD4+ T cells. We found that adding polyglycerol sulfate
to FN-triggered inflamed bronchial epithelium models reduced TSLP
expression and interleukin 6 secretion.

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