Regnase-1 plays an essential role in maintaining skin immune homeostasis via regulation of chemokine expression - 29/04/23
Abstract |
Regnase-1 is an endoribonuclease that regulates the stability of target genes. Here, we investigated whether Regnase-1 plays a regulatory role in the pathophysiology of atopic dermatitis, a chronic inflammatory skin disease. Regnase-1 levels were decreased in skin and serum of atopic dermatitis patients and mice. Regnase-1+/- mice exhibited more severe atopic dermatitis symptoms than wild-type mice in a house dust mite allergen-induced atopic dermatitis model. Regnase-1 deficiency led to the global changes in gene expression related with innate immune and inflammatory responses, in particular chemokines. The skin Regnase-1 level had an inverse relationship with chemokine expression when we analyzed samples of atopic dermatitis patients and Regnase-1-deficient mice, suggesting that potentiated chemokine production contributes to the augmented inflammation at lesion sites. Subcutaneous administration of recombinant Regnase-1 to mice significantly ameliorated atopic dermatitis-like skin inflammation with reduced chemokine production in a house dust mite-induced atopic dermatitis NC/Nga mouse model. These results indicate that Regnase-1 plays an essential role in maintaining skin immune homeostasis as a regulator of chemokine expression. Modulating Regnase-1 activity may be an efficient therapeutic strategy for treating chronic inflammatory diseases, including atopic dermatitis.
Le texte complet de cet article est disponible en PDF.Graphical Abstract |
Highlights |
• | Regnase-1 expression is decreased in skin and serum of atopic dermatitis patients. |
• | Regnase-1 deficiency is linked to aggravated inflammation in atopic dermatitis. |
• | Regnase-1 deficiency exacerbates chemokine expression in the lesional skin. |
• | Recombinant Regnase-1 ameliorates atopic dermatitis symptoms and chemokine production. |
• | Regnase-1 is an efficient therapeutic target for maintaining skin immune homeostasis. |
Keywords : Inflammation, Innate immunity, Endoribonuclease, Chemokine, Atopic dermatitis
Plan
Vol 162
Article 114558- juin 2023 Retour au numéroBienvenue sur EM-consulte, la référence des professionnels de santé.
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