RORα regulates the differential development of CD8+ memory subsets 4623

Abstract Description The establishment of immunological memory is crucial for antiviral immunity, forming the foundation of vaccine design and enhancing memory responses to combat infections. The retinoic acid receptor-related orphan receptor alpha (RORα), a member of the nuclear receptor family of ligand-regulated transcription factors, has emerged as a potential transcriptional regulator of CD8+ T cell immunity, though its role in these processes remains poorly understood. To explore this, we utilized a mouse model with T cell-specific RORα deletion which resulted in reduced cytotoxic T cell numbers, accompanied by higher LCMVARM titers in the spleen on day 5 post-infection, compared to wild-type controls. RORα deficiency also promoted T cell circulation leading to redistribution of cells into non-lymphoid tissues, specifically within the liver and adipose tissue during acute LCMV infections. Overall, RORα deficiency promotes the development of classical memory precursors (MP), periperal memory (TPM) and tissue-resident memory (TRM) cells. Taken together, these results suggest that the RORα promotes terminal effector (TE) cell formation and regulates effector function. Our study offers significant insights into the transcriptional regulation of CD8+ T cell differentiation. ?As a ligand-regulated transcription factor, these findings underscore the potential of RORα as a target for small molecule drugs that may enhance CD8+ T cell responses in the context of vaccines and adoptive cell therapies. Topic Categories Immune Response Regulation: Molecular Mechanisms (IRM)