Revealing the neuroimmune communication for better treatment outcomes in food allergy

Descripción del proyecto

Control neuroinmunológico de la alergia alimentaria y la respuesta a la inmunoterapia

El tratamiento de las alergias alimentarias se basa en la prevención y la intervención. La inmunoterapia oral a menudo no logra proporcionar una protección duradera. Con el apoyo de las acciones Marie Skłodowska-Curie, el proyecto AllergyREBELL investiga el papel de las células nerviosas intestinales en la regulación de las respuestas inmunitarias. Mediante el uso de técnicas avanzadas de imagen y multiómica espacial en modelos murinos, el proyecto traza un mapa de la compleja comunicación entre los sistemas nervioso e inmunitario en el intestino delgado. Esta investigación sobre cómo las señales neuronales influyen en el comportamiento de las células inmunitarias pretende arrojar luz sobre los motivos por los que las inmunoterapias tienen éxito o fracasan. En general, el proyecto busca traducir estos conocimientos en estrategias terapéuticas más seguras y eficaces.

Objetivo

Current management of potentially life-threatening food allergy (FA) relies on strict food avoidance and emergency medications such as ephedrine auto-injectors for acute reactions. Although oral allergen immunotherapy (OIT), gradual updosing of the offending food, has shown great promise in inducing oral tolerance, these effects are often transient and patients with severe initial symptoms are frequently non-responders. Thus, there is a pressing need for improved OIT protocols. Neuro-immune dialogue shapes the immune response in allergic asthma: activation of lung-innervating sensory neurons (nociceptors) by allergen exposure amplifies allergic lung inflammation. Comparably, gut-innervating nociceptors can also be activated through allergen exposure, pointing toward a similar neuro-immune dialogue in FA. It is currently unclear how nociceptors communicate with immune cells in FA and how this communication influences OIT outcome. In AllergyREBELL, I will identify crucial neuroimmune circuits for FA maintenance and tolerance induction by (1) constructing neuroimmune communication maps in the small intestine using a murine FA mouse model in combination with spatial transcriptomics, spatial lipidomics coupled to proteomics and intravital microscopy to track immune cell movements, (2) determining the modulatory capacity of neural factors using a sophisticated immune cell co-culture model and (3) characterising activation profiles of allergy-relevant nociceptors upon allergen exposure. This project will provide a multi-omics atlas on neuroimmune communication in FA as well as first insights how this communication modulates immune responses critical for tolerance induction. My paramount goal with AllergyREBELL is to identify crucial neuroimmune axes, which can be potentially exploited as therapeutic add-ons to improve OIT for non-responding patients and thus, increasing patients’ quality of life by reducing their constant fear of accidental exposures.