Fig. 1

Overview of the mechanisms of type 2 immune responses. Epithelial barrier disruption during exposure to allergens, bacteria, fungi, viruses and environmental epithelial barrier-damaging agents and inflammation can lead to the opening of the epithelial barrier and allow the penetration of allergens through tissues. In addition, microbial dysbiosis occurs with the colocalization of opportunistic pathogens and the loss of commensals. Damaged epithelial cells release chemokines and alarmins, which activate innate lymphoid cells and dendritic cells. Matured DCs migrate to local lymph nodes and present processed allergen peptides to naive T cells through MHC class II molecules. Naive T cells in the presence of IL-4 differentiate into Th2 cells. The type 2 cytokines IL-4, IL-5, IL-9 and IL-13 are produced not only by Th2 cells but also by ILC2s. IL-4 and IL-13 are involved in IgE class switching in B cells. IgE binds to FcεRI on the surface of mast cells and sensitizes them. The subsequent release of mast cell-associated mediators, such as histamine, tryptase, prostaglandins, leukotrienes and cytokines, induces goblet cell hyperplasia, smooth muscle contraction, and increased vascular permeability. IL-5 induces eosinophilia. Immunoregulatory cytokines, such as IL-10, TGF-β, and IL-35, released by T regulatory (Treg) cells can suppress type 2 as well as Th1, Th9 and Th-17 responses. IL-10-producing Breg cells also inhibit effector T cells. DC dendritic cells, EOS eosinophil, EPO eosinophil peroxidase, GM-CSF granulocyte‒macrophage colony‒stimulating factor, IL interleukin, ILC innate lymphoid cells, LT leukotriene, LTC4 leukotriene C4, MBP major basic protein, MC mast cells, PGD2 prostaglandin D2, TGF-β transforming growth factor-β, TSLP thymic stromal lymphopoietin