Genetics

This post reads Martin-Gutierrez and colleagues' 2024 Clinical and Experimental Immunology study through its LXR signalling paradox rather than its membrane phenotype. It follows why LXR-beta is the relevant isotype in T cells, the finding that NR1H2is strongly upregulated while LXR target genes and binding motifs are downregulated, the ligand-supply argument built from SREBF1 nuclear entry and the disturbed oxysterol synthesis and transport genes including an 8-fold drop in CYP27A1, which downstream targets fall, the two alternative explanations the authors test and rule out in T-cell activation and serum cytokines, and the two ligand experiments including the endogenous oxysterol agonist, closing on the interferon-beta normalization of four genes and the absence of these membrane changes in secondary progressive disease.