Immunological tolerance and regulation in Allergen-Specific Immunotherapy (AIT)

Allergen-Specific Immunotherapy (AIT) is currently the only available disease-modifying medical treatment with long-term clinical tolerance to natural allergen exposure in IgE-mediated allergic patients. Although AIT is well established, there are several limitations including adverse reactions, variable efficacy, and patient adherence to a long course of treatment. It induces desensitization through repetitive administration of allergen either subcutaneously or sublingually; oral immunotherapy has recently been approved, and new routes of administration such as intralymphatic and epicutaneous are being considered. AIT leads to an alteration of the immune response with suppression of allergic effector cells such as mast cells, eosinophils, and basophils, down-regulation of the allergen-specific Th2 dominated response toward a more Th1-like response; and the induction of regulatory T and B cells with suppressive capacity. Moreover, the release of anti-inflammatory cytokines such as IL-10 and TGF-β leads to the production of allergen-specific inducible Treg type 1. In addition, IL-10 increases human B-cell survival and proliferation. In addition, AIT induces allergen-specific IgG that can compete with IgE for allergen binding thereby decreasing allergen-induced effector cell activation.

The molecular and cellular mechanisms that lead to clinical benefits for patients have not been fully elucidated; thus, many questions concerning the changes and mechanisms of allergen-specific effector cells, allergen-specific blocking antibodies, innate lymphoid cells, and important B- and T-cell epitopes remain to be addressed.

The focus of this Research Topic is to present fundamental insights, translational potential, novel tools to refine in vitro and in vivo models, big data analysis, and new identification systems to define the principle of AIT-induced immunological tolerance in allergic patients. The ultimate goal is to stay informed on the latest innovations and products, antibodies, biologics, and recombinant particles.

We welcome the submission of reviews, mini-reviews, opinion, and original research articles that focus on, but are not strictly limited to, the following topics:
• Mechanisms and changes of allergen-specific T and B cells as well as allergen-specific regulatory T and B cells, allergen-specific IgE and blocking IgG antibodies, and B and T cell epitopes during AIT
• Suppression mechanisms of allergen-specific effector cells
• Role and mechanisms of antigen-presenting cells, innate lymphoid cells in AIT
• In vitro assays and in vivo models for preclinical analysis (to prevent IgE-mediated effector cell activation)
• Use of recombinant allergens, and antibodies in AIT

Topic Editor, Jamie M Orengo is an employee and shareholder of Regeneron Pharmaceuticals. Cate4rina Vizzardelli declares no competing interests with regard to this Research Topic.