IL-12, mainly produced by DCs, macrophages, and B lymphocytes,186 is a multifunctional immunoregulatory factor that can promote proliferation of Th1 and Th17 cells; improve the cytotoxicity of NK cells; and induce expression of IFN-γ in Th1 cells, NK cells, DCs, and macrophages via a positive feedback mechanism.187,188 Thus, IL-12 plays an aggressive role in CS by augmenting the activation of various immune cells. The gene discussed is IFNG; the disease is Cowden syndrome 1.