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Target intelligence / Profile preview
RAR-related orphan receptor gamma-t (RORγt)
- Target
- RORγt
- Molecular classification
- Nuclear receptor, Transcription factor, DNA-binding protein, Member of NR1 subfamily (nuclear receptors)
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Overview
RAR-related orphan receptor gamma-t (RORγt) is a DNA-binding transcription factor, a member of the nuclear receptor family, and an isoform of RORγ encoded by the RORC gene. RORγt expression is most prominent in immature CD4+ and CD8+ thymocytes and Th17 cells, where it acts as a lineage-defining factor for Th17 differentiation and survival, promoting production of pro-inflammatory cytokines such as IL-17A. RORγt also regulates lymphoid tissue organogenesis and has been implicated in the pathogenesis of several autoimmune disorders. Synthetic inhibitors targeting RORγt are being developed as potential therapeutics for autoimmune disease and inflammation. It is considered a validated therapeutic target, with its modulation posing both benefits and risks due to its critical immune regulatory roles.
- Other names
- RAR-related orphan receptor gamma-tRORγtRORgamma-TNuclear receptor ROR-gamma-tNuclear receptor subfamily 1 group F member 3 (NR1F3)
02
Mechanism of action
Inhibition of RORγt suppresses Th17 cell differentiation and IL-17A production, reducing autoimmunity and inflammation Inverse agonism at ligand-binding domain to block transcriptional activity indirectly
03
Biological functions
Differentiation and survival of T cells (especially Th17 cells)Regulation of lymphoid tissue organogenesis (lymph nodes, Peyer’s patches)Thymopoiesis (thymocyte development and inhibition of apoptosis)Immune response (drives differentiation toward Th17 lineage, promotes pro-inflammatory cytokine production)Regulation of apoptosis in undifferentiated T cellsCircadian rhythm regulation (less prominent for RORγt isoform)
04
Disease associations
Autoimmune diseases (psoriasis, rheumatoid arthritis, inflammatory bowel disease)Inflammation (central role in Th17-mediated pathology)Cancer (expression linked to tumorigenesis in some cancers)
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Safety considerations
Potential immunosuppression (compromising host defense by inhibiting Th17 responses)Risk of infections due to suppression of Th17-mediated immunity
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Interacting drugs
RORγt inverse agonists (experimental and in development)
1 more in the full profile.
07
Biomarkers
Th17 cell frequencyIL-17A levelsRORC gene transcript (Th17 cell-specific marker)
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