Key research advances in atopic dermatitis (AD) suggest the complexity of its endotypes. A comprehensive serum biomarker panel revealed at least 4 types of AD. Some represent classic TH2-dominant AD with filaggrin mutations commonly reported in Europeans, a simultaneously activated multipolar axis of cytokines often reported in Asian individuals, and an intrinsic type characterized by TH2 inferiority. Innate lymphoid cells, including natural killer cells, natural killer T cells, and fibroblasts, play a role in AD development and heterogeneity. Here, we discuss the endotypes of AD from the perspective of antigen types (hapten vs protein antigens), barrier function, and a novel set of immune cells. Endotypic stratification of AD may lead to the development of customized therapeutic strategies in the future. (J Allergy Clin Immunol 2021;148:1451-62.)
