Σφακιανάκης Αλέξανδρος
ΩτοΡινοΛαρυγγολόγος
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00302841026182
00306932607174
alsfakia@gmail.com

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Παρασκευή 20 Ιανουαρίου 2017

The Th2 gene cluster unraveled: Role of RHS6

Abstract

Although the transcription factors that regulate T helper (Th) type 2 cytokine production (IL-4, IL-5, and IL-13) are possible novel therapeutic targets, we lack a detailed understanding of the mechanisms that regulate the transcription of these cytokines. In this issue of Allergy, Hwang et al. studied the role of a specific DNA region (a cis-acting element called Rad50 hypersensitive site 6) RHS6, in the development of allergic airway inflammation. RHS6 is found in the Th2 cytokine "locus control region" but its role in activation of the IL-4, IL-5, and IL-13 genes was unknown. The authors here showed that RHS6 recruited the transcription factors GATA3, SATB1, and IRF4, each of which are involved in transcription of all three Th2 cytokine genes. Indeed genetic deficiency in RHS6 inhibited expression of IL-4, IL-5, and IL-13 and reduced allergic airway inflammation in a murine model of ovalbumin-induced sensitization. Deletion of RHS6 also inhibited formation of the transcription factor complex of GATA3, SATB1, and IRF4 that reduced the transcription of IL-4, IL-5, and IL-13. This study suggests that RHS6 is critical for the development of allergic airway inflammation and that the GATA3, SATB1, IRF4 and RHS6 complex maybe a potential therapeutic target for the treatment of asthma.

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