Nuclear receptor LXRβ controls fitness and functionality of activated T cells Journal Article
| Authors: | Michaels, A. J.; Campbell, C.; Bou-Puerto, R.; Rudensky, A. Y. |
| Article Title: | Nuclear receptor LXRβ controls fitness and functionality of activated T cells |
| 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. © 2020 Michaels et al. |
| Journal Title: | Journal of Experimental Medicine |
| Volume: | 218 |
| Issue: | 4 |
| ISSN: | 0022-1007 |
| Publisher: | Rockefeller University Press |
| Date Published: | 2021-04-05 |
| Start Page: | e20201311 |
| Language: | English |
| DOI: | 10.1084/jem.20201311 |
| PUBMED: | 33373442 |
| PROVIDER: | scopus |
| PMCID: | PMC7774588 |
| DOI/URL: | |
| Notes: | Article -- Export Date: 1 February 2021 -- Source: Scopus |
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