| First Author | Michaels AJ | Year | 2021 |
| Journal | J Exp Med | Volume | 218 |
| Issue | 4 | PubMed ID | 33373442 |
| Mgi Jnum | J:343862 | Mgi Id | MGI:6724797 |
| Doi | 10.1084/jem.20201311 | Citation | Michaels AJ, et al. (2021) Nuclear receptor LXRbeta controls fitness and functionality of activated T cells. J Exp Med 218(4) |
| abstractText | T cells increase cholesterol biosynthesis upon activation to generate substrates for cellular growth and proliferation. The ubiquitously expressed liver X receptor beta (LXRbeta) 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 LXRbeta 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 LXRbeta-deficient effector T cells, suggesting that the heightened immune activation in mice harboring LXRbeta-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 LXRbeta function in immune homeostasis and provides a basis for immunological therapies through targeting of this receptor. |
