HMOS 2'FL and 3FL prevent house dust mite induced proinflammatory cytokine release and decrease specific IgE production in a murine allergic asthma model.

Introduction: Allergic asthma is characterized by sensitization to airborne allergens like house dust mite (HDM). Human milk oligosaccharides (HMOS) are linked to improved immune maturation and potentially alleviate allergy development.

Methods: A human model for crosstalk between bronchial epithelial cells (BECs), monocyte-derived DCs (moDCs) and T cells, during HDM exposure, was established. The immunomodulatory effects of the HMOS 2'-fucosyllactose (2'FL) and 3-fucosyllactose (3FL) were investigated in this model and subsequently in a house dust mite-induced allergic asthma murine model.

Results: HDM exposure during BEC-DC coculture enhanced type 2 instructing TSLP, while reducing regulatory TGFβ secretion. Coculture of HDM-primed DCs with T cells enhanced IL4 secretion. 2'FL or 3FL preincubation prevented HDM-induced TSLP and IL8 release from BEC-DC. HDM-allergic mice receiving a 1% 2'FL or 0,5% 3FL supplemented diet both had lower serum levels of HDM-specific IgE compared to mice fed control diet. In conclusion, a human coculture model for HDM-induced BEC-DC activation and subsequent type 2 T cell response was established. 2'FL or 3FL preincubation of BEC-DC prevented HDM-induced activation and modified downstream T cell responses . Both HMOS reduced HDM-specific IgE in a murine model for HDM allergic asthma, but did not protect against airway inflammation.

Conclusion: Here, we describe an human airway mucosal HDM sensitization model as relevant tool to reduce use of animals in studies aiming to prevent HDM allergic asthma. Both as well as , HMOS were found to drive away from a type 2 immune signature, paving the way to further investigate the potential allergy preventive effects of fucosylated HMOS.