ILC2s in skin disorders

The activation of group 2 innate lymphoid cells (ILC2s) is controlled by various tissue-derived factors, including cytokines, whereas T cells respond to foreign antigens. This review discusses the tissue-specific properties of ILC2s in skin and their involvement in human skin diseases. In a steady state, cutaneous ILC2s contribute to tissue homeostasis. In the keratinocytes of patients with atopic dermatitis (AD), the inflammatory cytokine interleukin-33 (IL-33) is overexpressed. ILC2s are stimulated by IL-33-stimulated basophils through IL-4 to produce type 2 cytokines, such as IL-5 and IL-13. According to several studies, ILC2 expression is upregulated in human AD skin lesions, and it is involved in AD pathogenesis. Dupilumab, an antibody against IL-4 receptor α, lowered the number and percentage of ILC2s in the peripheral blood of patients with AD. Cutaneous ILC2s are divided into two subgroups: circulating and skin-resident ILC2s. However, ILC2s are homogeneous cell populations that are highly diverse and plastic, and there is no consensus on the classification that should be used. The variations in the definition for cutaneous ILC2s in different studies make comparisons among studies difficult, and in particular, the weak expression of the IL-33 receptor ST2 in cutaneous ILC2s and its lack of markers have posed a great challenge to researchers. Therefore, further comprehensive analytical studies are warranted.