Method for treating t- helper type 2 mediated disease

The present invention relates to the treatment of T- helper type 2 (Th2)-mediated disease. Here, the inventors set out to investigate at the genome level the effects of SETDB1- dependent H3K9me3 deposition on CD4 T cell activation, differentiation and commitment. By using conditional Setdb1-/- mice, they show that SETDB1 restricts Th1 cell priming and ensures Th2 cell integrity. Unlike their wild-type counterparts, SETDB1-deficient Th2 cells readily express the entire Th1 gene network when exposed to the Th1-instructing cytokine IL12. More, SETDB1 methylates H3K9 at a subset of ERVs that flank and repress Th1 enhancers or behave themselves as cis-regulatory elements of a large network of Th1 genes, including Ifng, Stat4, Runx3 and Tbx21. Therefore, H3K9me3 deposition by SETDB1 locks the Th1 gene expression program and thus ensures T cell lineage integrity by repressing a repertoire of ERVs that have been co-opted to behave as Th1 lineage-specific cis-regulatory modules. Thus, the invention relates to a SETDB1 inhibitor for use in a method for increasing the Th1/Th2 ratio of an immune response in a subject in need thereof.

Keywords: Asthma
AdoueV. et al. Immunity (2019) 50(3):629-644



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Aymeric Empereur
Aymeric Empereur
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