Ror-gamma T inhibition as a Pharmacological Approach for Inflammatory Bowel Disease

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Leo Robert Fitzpatrick


Retinoic Acid Related Orphan Nuclear Receptor gamma T (ROR-γT) is the lineage specifying transcription factor for IL-17 expressing cells. ROR-γT expression is up-regulated in various animal models of colitis, as well as in certain patients with Inflammatory Bowel Disease (IBD). Transfer of ROR-gamma null T cells to RAG1 deficient mice did not induce colitis in these animals. Recently, data with a specific small molecule inhibitor (VPR-7) of ROR-γT showed efficacy in a murine model of IBD.  In principle, ROR-γT inhibitors would specifically inhibit Th17 cell differentiation and expansion. ROR-γT, which is functioning in innate intestinal lymphoid cells, may also be a target for ROR-γT inhibitors. These drugs would block the transcription of possible pro-inflammatory receptors (IL-23R) cytokines (IL-17, IL-21) and chemokines (CCL20) putatively involved in the pathogenesis of IBD. Off-target effects of ROR-γT inhibitors have been reported, including the inhibition of colonic IL-23 in a mouse model of colitis. Several pharmaceutical companies are actively involved in the development of specific inhibitors targeting ROR-γT. It is possible that ROR-γT inhibitors will enter clinical trials for the treatment of IBD in the near future. 

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FITZPATRICK, Leo Robert. Ror-gamma T inhibition as a Pharmacological Approach for Inflammatory Bowel Disease. Medical Research Archives, [S.l.], v. 2, n. 2, aug. 2015. ISSN 2375-1924. Available at: <>. Date accessed: 17 oct. 2017.
Ror-Gama T, Colitis, Mice, Inflammatory Bowel Disease
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