Post-translational regulation of RORγt-A therapeutic target for the modulation of interleukin-17-mediated responses in autoimmune diseases

Retinoic acid-related orphan receptor gamma t (ROR gamma t) is a nuclear receptor, which is selectively expressed by various lymphocytes. RORyt is critical for the development of secondary and tertiary lymphoid organs, and for the thymic development of the T cell lineage. ROR gamma t 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 ROR gamma t is tightly controlled. By its nature as a nuclear receptor, ROR gamma t 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 ROR gamma t function. Here we attempt a comprehensive review of the post-translational regulation of ROR gamma t, an area that holds the potential to transform the way we target the ROR gamma t/IL-17 pathway, by enabling the development of safe and highly selective modulators of ROR gamma t activity. (C) 2016 The Authors. Published by Elsevier Ltd.