Post-translational regulation of RORγt—A therapeutic target for the modulation of interleukin-17-mediated responses in autoimmune diseases. (August 2016)

• Record Type: Journal Article
• Authors: Rutz, Sascha; Eidenschenk, Celine; Kiefer, James R.; Ouyang, Wenjun
• Is Part Of: Cytokine & growth factor reviews. Volume 30(2016)
• Page Start: 1
• Page End: 17
• Publication Date: 2016-08
• Subjects: Retinoic acid-related orphan receptor gamma -- Nuclear receptor -- Interleukin-17 -- Inverse agonist -- Ubiquitinylation -- Posttranslational regulation; Cytokines -- Periodicals; 571.84
• DOI: 10.1016/j.cytogfr.2016.07.004
• Languages: English
• ISSNs: 1359-6101

Abstract

Graphical abstract: Post-translational regulation of RORγt. Highlights: RORγt is the master transcription factor of IL-17 expression and Th17 cells. As a nuclear receptor, RORγt activity is also regulated in a ligand-dependent manner. Multiple post-translational modifications, such as acetylation and ubiquitinylation, as well as interactions with various co-factors, modulate RORγt function. Abstract: Retinoic acid-related orphan receptor gamma t (RORγt) is a nuclear receptor, which is selectively expressed by various lymphocytes. RORγt is critical for the development of secondary and tertiary lymphoid organs, and for the thymic development of the T cell lineage. RORγt has been extensively studied as the master transcription factor of IL-17 expression and Th17 cells, which are strongly associated with various inflammatory and autoimmune conditions. Given its essential role in promoting pro-inflammatory responses, it is not surprising that the expression of RORγt is tightly controlled. By its nature as a nuclear receptor, RORγt activity is also regulated in a ligand-dependent manner, which makes it an attractive drug target. In addition, multiple post-translational mechanisms, including post-translational modifications, such as acetylation and ubiquitinylation, as well as interactions with various co-factors, modulate RORγt function. Here we attempt a comprehensive review of the post-translational regulation of RORγt, an area that holds the potential to transform the way we target the RORγt/IL-17 pathway, by enabling the development of safe and highly selective modulators of RORγt activity.