Anti-inflammatory effects of polyglycerol sulfates and natural polyanions in type 2 inflammation

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 lymphoprotein (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.