The gut environment as an instructor of immune tolerance and allergy development

Rationale: The human immune system shows interindividual immune variation that relates to genetic differences as well as environmental exposures.

The general purpose of our work is to study how our closest environment – gut microbes and microbial factors - are involved in immune modulation, whether this impacts allergy or tolerance, and by what mechanisms this takes place.

We will investigate this: ex vivo in cohort materials, in vitro in experimental studies, and in tissue/in vivo using cellular systems, organoids, and murine models.Specific aims: We studyTh-cell fates and monocyte/DC characteristics during allergy- and tolerance development in relation to the gut environment are studied in material from a unique clinical cohort of children undergoing oral immunotherapy against peanut.Microbe-mediated immune modulation and regulation.

Here we delineate mechanisms, with a focus on extracellular membrane vesicles (EMVs) and their immunomodulatory capacities in myeloid cells.Cell-, organoid- and in vivo models for proof-of concept studies.

Here we turn to gut model systems to study observed associations and mechanisms revealed above in a tissue setting and how bacteria-derived vesicles can pass the gut barrier.Importance: Our proposed project is translational and will use cutting-edge methodology to provide an improved and deeper understanding of how the infant immune system and gut environment promote allergy and tolerance, with possible implications for clinical praxis.