RORα in T_reg cells

Sci. Immunol. 3, eeao6923 (2018)

Atopic dermatitis is an inflammatory skin disease characterized by type 2 cytokines and eosinophilia. In Science Immunology, Malhotra et al. report that skin-resident regulatory T cells (T_reg cells) require the transcription factor RORα to suppress skin inflammation mediated by type 2 innate lymphoid cells (ILC2s) and CD4⁺ type 2 helper T cells (T_H2 cells). Transcriptomics reveals high expression of the gene encoding RORα in skin-resident T_reg cells of mice and humans. T_reg cell–specific loss of Rora increases expression of the cytokine IL-5 and chemokine CCL8 in allergen-induced skin lesions. Skin T_reg cells express DR3, a member of the cytokine TNF receptor superfamily, sequesters the DR3 ligand TL1A and prevents potentiation of IL-33 by TL1A, thereby limiting the ability of ILC2s to express IL-5. Thus, RORα-dependent expression of DR3 in skin-resident T_reg cells limits allergic skin inflammatory responses.