RORα-expressing T regulatory cells restrain allergic skin inflammation

Area of Science:

• Immunology
• Dermatology
• Molecular Biology

Background:

• Atopic dermatitis involves type 2 cytokines, ILC2s, T_H2 cells, and eosinophilia.
• Skin-resident T regulatory cells (Tregs) play a role in managing allergic skin inflammation.

Purpose of the Study:

• To investigate the role of retinoid-related orphan receptor alpha (RORα) in skin-resident Tregs in atopic dermatitis.
• To elucidate the molecular mechanisms by which RORα influences allergic skin inflammation.

Main Methods:

• Utilized two distinct mouse models of atopic dermatitis.
• Performed targeted deletion of RORα in mouse Tregs.
• Analyzed cytokine production (IL-5, IL-4) and cell activation markers (DR3, TL1A).

Main Results:

• Deletion of RORα in Tregs led to increased eosinophilia driven by ILC2s and T_H2 cells.
• RORα expression in Tregs suppressed IL-4 and enhanced DR3 expression, a receptor for TL1A.
• Loss of RORα impaired Treg ability to sequester TL1A, enhancing ILC2 activation.

Conclusions:

• RORα in skin-resident Tregs is crucial for controlling allergic skin inflammation in atopic dermatitis.
• The TL1A-DR3 signaling pathway is modulated by RORα in Tregs.
• RORα and the TL1A-DR3 circuit represent potential therapeutic targets for atopic dermatitis.