| First Author | Banerjee D | Year | 2016 |
| Journal | Immunology | Volume | 147 |
| Issue | 4 | Pages | 399-413 |
| PubMed ID | 26694902 | Mgi Jnum | J:253096 |
| Mgi Id | MGI:5924589 | Doi | 10.1111/imm.12570 |
| Citation | Banerjee D, et al. (2016) Small molecule mediated inhibition of RORgamma-dependent gene expression and autoimmune disease pathology in vivo. Immunology 147(4):399-413 |
| abstractText | Retinoic acid receptor-related orphan nuclear receptor gamma (RORgamma) orchestrates a pro-inflammatory gene expression programme in multiple lymphocyte lineages including T helper type 17 (Th17) cells, gammadelta T cells, innate lymphoid cells and lymphoid tissue inducer cells. There is compelling evidence that RORgamma-expressing cells are relevant targets for therapeutic intervention in the treatment of autoimmune and inflammatory diseases. Unlike Th17 cells, where RORgamma expression is induced under specific pro-inflammatory conditions, gammadelta T cells and other innate-like immune cells express RORgamma in the steady state. Small molecule mediated disruption of RORgamma function in cells with pre-existing RORgamma transcriptional complexes represents a significant and challenging pharmacological hurdle. We present data demonstrating that a novel, selective and potent small molecule RORgamma inhibitor can block the RORgamma-dependent gene expression programme in both Th17 cells and RORgamma-expressing gammadelta T cells as well as a disease-relevant subset of human RORgamma-expressing memory T cells. Importantly, systemic administration of this inhibitor in vivo limits pathology in an innate lymphocyte-driven mouse model of psoriasis. |
