The role of Treg cell subsets in allergic disease.

Allergic diseases are caused by a hypersensitivity reaction to an external substance that is normally not harmful to the body. An imbalance between type 2 immune response and regulatory T cells (Tregs) has been found to be effective in immunopathology of allergic diseases. Tregs can inhibit type 2 immune cells such as T helper 2 (Th2), type 2 innate lymphoid cells and IgE-producing B cells; meanwhile, they induce tolerogenic dendritic cells, regulatory B cells and IgG4-producing B cells. Tregs play a critical role in maintaining immune tolerance to allergens that regulate the type 2 immune response in patients with allergic diseases. Allergen-specific immunotherapy (AIT) is the only causal treatment modality to reduce allergic symptoms by altering the immune response to allergens. A key feature of AIT is to induce and maintain immune tolerance to allergens that enhances functionality, while inducing and maintaining Tregs in allergic patients. In this review, we discuss the six subsets of Tregs, natural (nTregs), inducible Treg (iTregs), inducible costimulatory (ICOS+ Tregs), Tr1, CD8+ Tregs and IL-17-producing Tregs, and their role in allergic disease and allergen immune tolerance. We also discuss specific markers of dysregulated Tregs in allergy such as, immunoglobulin-like transcript (ILT) 3, chemoattractant receptor-homologous molecule expressed on Th2 cells (CRTH2) and ST2. These novel molecules on Tregs provide an opportunity for novel treatment strategies aimed at changing the function of Tregs in allergic diseases.