Fig. 8

KDM6A/B inhibition in respiratory syncytial virus infection. Respiratory syncytial virus (RSV) infection is associated with the activation of dendritic cells (DCs), which promote a T helper 2 (Th2)-type response and a microenvironment within the lungs permissive for the recruitment of inflammatory cells, including macrophages, T cells and dendritic cells. DC activation by RSVs is accompanied by upregulation of the H3K27-specific demethylases KDM6A/B and a consequent decrease in H3K27 trimethylation (H3K27me3). Inhibition of KDM6A/B with GSK-J4 impairs the ability of DCs to present antigens to and activate Th2 cells through the downregulation of antigen-presenting MHC class II (MHC-II) and the costimulatory CD80/C86 molecules. GSK-J4 also inhibits the production of the pro-inflammatory cytokines and chemokines CCL2, CCL3, CCL5 and IL-6 by DCs to reduce the ingress of inflammatory cells into the lungs and attenuate the pulmonary immunopathology associated with the RSV infection. This figure was adapted from Malinczak et al. (2020) [77] and created in BioRender.com