Brd4 Regulates the Homeostasis of CD8⁺ T-Lymphocytes and Their Proliferation in Response to Antigen Stimulation.

ABSTRACT: CD8⁺ T cells are major components of adaptive immunity and confer robust protective cellular immunity, which requires adequate T-cell numbers, targeted migration, and efficient T-cell proliferation. Altered CD8⁺ T-cell homeostasis and impaired proliferation result in dysfunctional immune response to infection or tumorigenesis. However, intrinsic factors controlling CD8⁺ T-cell homeostasis and immunity remain largely elusive. Here, we demonstrate the prominent role of Brd4 on CD8⁺ T cell homeostasis and immune response. By upregulating Myc and GLUT1 expression, Brd4 facilitates glucose uptake and energy production in mitochondria, subsequently supporting naïve CD8⁺ T-cell survival. Besides, Brd4 promotes the trafficking of naïve CD8⁺ T cells partially through maintaining the expression of homing receptors (CD62L and LFA-1). Furthermore, Brd4 is required for CD8⁺ T cell response to antigen stimulation, as Brd4 deficiency leads to a severe defect in clonal expansion and terminal differentiation by decreasing glycolysis. Importantly, as JQ1, a pan-BRD inhibitor, severely dampens CD8⁺ T-cell immune response, its usage as an anti-tumor agent or latency-reversing agent for human immunodeficiency virus type I (HIV-1) should be more cautious. Collectively, our study identifies a previously-unexpected role of Brd4 in the metabolic regulation of CD8⁺ T cell-mediated immune surveillance and also provides a potential immunomodulation target.

SUBMITTER: Peng Z 

PROVIDER: S-EPMC8427756 | biostudies-literature |

REPOSITORIES: biostudies-literature