Understanding Neonatal Induction of Proallergic T Follicular Helper Cells

Key Words: Neonates, Allergy, T follicular helper cells, IgE, Dysbiosis, Peanut antigen

Allergies to food and environmental antigens have reached epidemic proportions, with worldwide sensitization among children approaching 40-50%. Antibodies are made by an immune cell type called as B lymphocytes. Different classes of antibodies perform distinct biological functions ranging from beneficial, such as neutralizing pathogens and maintaining gut homeostasis, to the harmful, such as involvement in autoimmune disorders and allergies. The IgE class of antibodies is a key mediator of allergic disease. Crosslinking of IgE molecules on the surface of mast cells by allergens can have devastating consequences when it results in anaphylaxis, a rapid, severe form of life-threatening allergic reaction. The production of anaphylactic IgE by B cells to allergens is dependent on help from yet another immune cell called the T cell. The precise nature of this T cell was hitherto unknown. Using an array of genetic mouse models of allergy, we had recently discovered a novel T follicular helper cell subset that help B cells make anaphylactic IgE to allergens.

Allergies, particularly to food antigens, often manifests at a very early age. While the proclivity of food sensitization in children has been attributed urbanization and modern lifestyle, including rampant use of antibiotics, the precise immunological mechanisms for this bias remain ill-defined. Our preliminary data with mouse models of sensitization suggests that perinatal mice have an intrinsic bias towards the generation of allergy promoting T follicular helper cell subset induction. Further, our clinical data also shows that these proallergic T cells are found to be present in children with peanut allergy but not healthy individuals. In addition to this we also find that an antibiotic-induced perturbation of the gut microbiome in mice also enhances these proallergic T cells generation. The goal of the proposal is to identify the immunological and environmental determinants of proallergic T follicular helper cell induction bias seen in neonates. If successful, our work could inform future therapies to manipulate proallergic T follicular helper cells and thus could mitigate allergic sensitization in children.