Krage Clemens, Malek Mohammadi Nouri Peyman, Dernedde Jens, Kizhakkedathu Jayachandran N, Hedtrich Sarah, Haag Rainer, Achazi Katharina
Institute für Chemie und Biochemie, Freie Universität Berlin, Takustrasse 3, D-14195 Berlin, Germany.
Centre for Blood Research, Life Sciences Institute, University of British Columbia, 2350 Health Sciences Mall, Life Sciences Centre, Vancouver, British Columbia V6T 1Z3, Canada.
Biomacromolecules. 2025 Jun 9;26(6):3819-3829. doi: 10.1021/acs.biomac.5c00420. Epub 2025 May 23.
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 (T2) 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.
2型炎症是先天性和适应性免疫系统的一种重要防御机制，但如果调节失调，它会引发慢性过敏性疾病，如过敏性哮喘和特应性皮炎。胸腺基质淋巴细胞生成素（TSLP）通过引导T细胞向2型辅助性T细胞（T2）亚型分化并刺激B细胞产生抗体，从而促进2型炎症。最近发现，特应性皮炎患儿血浆中的纤连蛋白（FN）水平升高，并且在支气管上皮组织模型中显示出潜在的促炎作用。这两种蛋白质的表面电荷表明它们可能与带电分子相互作用。为了寻找对抗2型炎症的新策略，我们发现带负电荷的聚甘油硫酸盐能与TSLP和FN紧密结合。我们证实，这些分子通过减少TSLP介导的CD4 T细胞2型极化来抑制炎症。我们发现，在FN引发的炎症性支气管上皮模型中添加聚甘油硫酸盐可降低TSLP表达和白细胞介素6的分泌。
