Modulators of retinoid-related orphan receptor gamma

Abstract

Methods for modulating (inhibiting or stimulating) retinoid-related orphan receptor γ (RORγ) activity. This modulation has numerous effects, including inhibition of T H -17 cell function and/or T H -17 cell activity, and inhibition of re-stimulation of T H -17 cells, which are beneficial to treatment of inflammation and autoimmune disorders. Stimulation of RORγ results in stimulation of T H -17 cell function and/or activity which is beneficial for immune-enhancing compositions (e.g., vaccines).

What is claimed is: 
     
         1 . A method of inducing T H -17 cell differentiation, function or activity in an individual in need thereof, comprising administering to said individual an effective amount of a small organic molecule agonist of RORγ, wherein said small organic molecule agonist has a molecular weight of less than about 600 daltons, wherein said small organic molecule agonist has the ability to enhance transcription from a Gal4 construct comprising a human RORγ ligand binding domain in a Chinese hamster ovary host cell. 
     
     
         2 . The method of  claim 1 , wherein said T H -17 cell function or activity is release of a cytokine. 
     
     
         3 . The method of  claim 2 , wherein said cytokine is interleukin-17 or interleukin-22. 
     
     
         4 . The method of  claim 1 , wherein the RORγ agonist is orally administered. 
     
     
         5 . The method of  claim 1  wherein the RORγ agonist is locally administered. 
     
     
         6 . The method of  claim 1 , wherein said RORγ agonist is OR-12872 or OR-942. 
     
     
         7 . The method of  claim 1 , wherein the small organic molecule agonist is administered in an amount effective to increase mucosal immunity in the individual. 
     
     
         8 . The method of  claim 1 , wherein the small organic molecule agonist is administered in an amount effective to increase the immunogenicity of a vaccine administered to the individual. 
     
     
         9 . The method of  claim 1 , wherein the small organic molecule agonist is administered in an amount effective to increase the number of T cells reactive to an antigen.