Schematic representation of NFATC2 contributions to the severity of anaphylaxis. NFATC2 deficiency leads to an attenuated Th2 response, resulting in less secretion of IL-4 and other Th2 cytokines. This attenuated cytokine response leads to lower antibody levels, and the decrease in total IgE reduces the FcεRI expression on basophils and mast cells. The decreased FcεRI expression and lower plasma IgE level lead to less cell-associated IgE and decreased basophil/mast cell degranulation upon antigen exposure. Similarly, the decrease in anti-ASNase IgG antibodies results in fewer ASNase ICs upon antigen exposure and decreased IgG/FcγRIII-mediated anaphylaxis. Furthermore, the decrease in IL-4 secretion caused by NFATC2 deficiency limits the severity of histamine-induced anaphylaxis. PAF, platelet-activating factor.