It Takes Guts to Regulate Nuclear Receptors - Testing Your Mettle!-It Takes Guts to Regulate Nuclear Receptors

Video Transcription

Video Summary

Video 1 Summary:<br /><br />The speaker discusses the role of ROR-alpha in TH17 cells and its potential as a therapeutic target for inflammatory bowel disease (IBD). ROR-alpha regulates the development and function of TH17 cells, with overexpression leading to increased TH17 cells and knockout decreasing IL-17 expression. The speaker highlights that targeting ROR-alpha may be a safer approach compared to targeting ROR-gamma. Knockout of ROR-alpha in T cells in a mouse model of colitis provides protection from disease and decreased pro-inflammatory cytokine expression, suggesting ROR-alpha's importance in TH17 phenotype stability and IL-17 expression.<br /><br />Credits: None mentioned.<br /><br />Video 2 Summary:<br /><br />The speaker discusses their research on finding new nuclear receptor ligands affecting gut-brain signaling. They identified hydroxyl form of DHA called 7-HDHA as a high-affinity ligand for PPAR-alpha, which increases neuro-arborization and plasticity in cortical neurons. They also found new ligands for PPAR-alpha from the human gut microbiome, including hydroxylated derivative of stearic acid known as 10-HSA. These ligands have potential therapeutic applications, especially for diseases like IBD. Patients with IBD showed variable levels of these microbiome-derived ligands, and further investigation aims to understand the relationship between ligand levels, microbial composition, and disease severity. Future plans include studying the effects of these ligands on IBD in preclinical models and exploring their use as probiotics or dietary supplements.<br /><br />Credits: None mentioned.

Keywords

ROR-alpha

TH17 cells

therapeutic target

inflammatory bowel disease

IL-17 expression

ROR-gamma

colitis

pro-inflammatory cytokine

phenotype stability

nuclear receptor ligands

gut-brain signaling

PPAR-alpha


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