{Reference Type}: Journal Article
{Title}: Nuclear receptor LXRβ controls fitness and functionality of activated T cells.
{Author}: Michaels AJ;Campbell C;Bou-Puerto R;Rudensky AY;
{Journal}: J Exp Med
{Volume}: 218
{Issue}: 4
{Year}: 04 2021 5
{Factor}: 17.579
{DOI}: 10.1084/jem.20201311
{Abstract}: T cells increase cholesterol biosynthesis upon activation to generate substrates for cellular growth and proliferation. The ubiquitously expressed liver X receptor β (LXRβ) encoded by the Nr1h2 gene is a critical regulator of cholesterol homeostasis in mammalian cells; however, its cell-intrinsic role in T cell biology remains poorly understood. We report that ablation of LXRβ in T cells leads to spontaneous T cell activation and T lymphocytopenia. Unexpectedly, analysis of mixed bone marrow chimeric mice revealed a cell-autonomous survival defect that reduced the fitness of LXRβ-deficient effector T cells, suggesting that the heightened immune activation in mice harboring LXRβ-deficient T cells was due to impaired regulatory T (T reg) cell functionality. Indeed, we found that single-copy deletion of Nr1h2 in T reg cells disrupted activated T reg cell metabolism and fitness and resulted in early-onset fatal autoimmune disease. Our study demonstrated an indispensable requirement for T reg cell-intrinsic LXRβ function in immune homeostasis and provides a basis for immunological therapies through targeting of this receptor.