Suppression of Hippo Pathway by Food Allergen Exacerbates Intestinal Epithelia Instability and Facilitates Hypersensitivity

Scope:Hippo signaling is a crucial pathway in innate immune responses, but the relationship between food allergy and Hippo pathway is unknown. The aim of this work is to investigate the regulation of food allergy by Hippo pathway and reveal the molecular mechanisms.

Methods and results:Two food allergens tropomyosin and ovalbumin are used to challenge a mouse model and CMT93 intestinal epithelia cell model. The allergic responses and the activation of Hippo pathway are tested in these models. In the mouse model, both allergens trigged significant allergic responses, and Hippo pathway is suppressed after allergen challenge. In CMT93, both allergens upregulate the expression of allergic cytokines thymic stromal lymphopoietin, interleukin (IL)-25, and IL-33. In TAZ KD CMT93, the Hippo pathway is blocked, and the expression of allergenic cytokines are also suppressed.

Conclusions:Both in vivo and in vitro data demonstrate that the two food allergens suppressed Hippo pathway by downregulating TAZ expression, resulting in intestinal epithelia instability, and finally leading to hypersensitivity reactions. These findings provide potential therapeutic targets and molecular markers for food allergy, and provide dietary guidelines for allergenic individuals.