RORα-expressing T regulatory cells restrain allergic skin inflammation.
Fiche publication
Date publication
mars 2018
Journal
Science immunology
Auteurs
Membres identifiés du Cancéropôle Est :
Pr CHAMBON Pierre
Tous les auteurs :
Malhotra N, Leyva-Castillo JM, Jadhav U, Barreiro O, Kam C, O'Neill NK, Meylan F, Chambon P, von Andrian UH, Siegel RM, Wang EC, Shivdasani R, Geha RS
Lien Pubmed
Résumé
Atopic dermatitis is an allergic inflammatory skin disease characterized by the production of the type 2 cytokines in the skin by type 2 innate lymphoid cells (ILC2s) and T helper 2 (T2) cells, and tissue eosinophilia. Using two distinct mouse models of atopic dermatitis, we show that expression of retinoid-related orphan receptor α (RORα) in skin-resident T regulatory cells (T) is important for restraining allergic skin inflammation. In both models, targeted deletion of RORα in mouse T led to exaggerated eosinophilia driven by interleukin-5 (IL-5) production by ILC2s and T2 cells. Expression of RORα in skin-resident T suppressed IL-4 expression and enhanced expression of death receptor 3 (DR3), which is the receptor for tumor necrosis factor (TNF) family cytokine, TNF ligand-related molecule 1 (TL1A), which promotes T functions. DR3 is expressed on both ILC2s and skin-resident T Upon deletion of RORα in skin-resident T, we found that T were no longer able to sequester TL1A, resulting in enhanced ILC2 activation. We also documented higher expression of RORα in skin-resident T than in peripheral blood circulating T in humans, suggesting that RORα and the TL1A-DR3 circuit could be therapeutically targeted in atopic dermatitis.
Mots clés
Animals, Dermatitis, Atopic, immunology, Female, Humans, Immunity, Innate, Mice, Transgenic, Nuclear Receptor Subfamily 1, Group F, Member 1, immunology, Receptors, Tumor Necrosis Factor, Member 25, immunology, Skin, immunology, T-Lymphocytes, Regulatory, immunology, Tumor Necrosis Factor Ligand Superfamily Member 15, immunology
Référence
Sci Immunol. 2018 Mar 2;3(21):