{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,22]],"date-time":"2026-10-22T04:58:53Z","timestamp":1792645133486,"version":"4.5.0"},"reference-count":66,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2021,8,26]],"date-time":"2021-08-26T00:00:00Z","timestamp":1629936000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100012659","name":"Foundation for Innovative Research Groups of the National Natural Science Foundation of China","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100012659","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100015809","name":"Health Medical Collaborative Innovation Program of Guangzhou","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100015809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100012503","name":"Dream Project of Ministry of Science and Technology of the People\u2019s Republic of China","doi-asserted-by":"publisher","award":["2017ZX10202102"],"award-info":[{"award-number":["2017ZX10202102"]}],"id":[{"id":"10.13039\/501100012503","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Immunol."],"abstract":"<jats:p>\n                    CD8\n                    <jats:sup>+<\/jats:sup>\n                    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\n                    <jats:sup>+<\/jats:sup>\n                    T-cell homeostasis and impaired proliferation result in dysfunctional immune response to infection or tumorigenesis. However, intrinsic factors controlling CD8\n                    <jats:sup>+<\/jats:sup>\n                    T-cell homeostasis and immunity remain largely elusive. Here, we demonstrate the prominent role of Brd4 on CD8\n                    <jats:sup>+<\/jats:sup>\n                    T cell homeostasis and immune response. By upregulating Myc and GLUT1 expression, Brd4 facilitates glucose uptake and energy production in mitochondria, subsequently supporting na\u00efve CD8\n                    <jats:sup>+<\/jats:sup>\n                    T-cell survival. Besides, Brd4 promotes the trafficking of na\u00efve CD8\n                    <jats:sup>+<\/jats:sup>\n                    T cells partially through maintaining the expression of homing receptors (CD62L and LFA-1). Furthermore, Brd4 is required for CD8\n                    <jats:sup>+<\/jats:sup>\n                    T cell response to antigen stimulation, as\n                    <jats:italic>Brd4<\/jats:italic>\n                    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\n                    <jats:sup>+<\/jats:sup>\n                    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\n                    <jats:sup>+<\/jats:sup>\n                    T cell-mediated immune surveillance and also provides a potential immunomodulation target.\n                  <\/jats:p>","DOI":"10.3389\/fimmu.2021.728082","type":"journal-article","created":{"date-parts":[[2021,8,31]],"date-time":"2021-08-31T08:04:37Z","timestamp":1630397077000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":12,"title":["Brd4 Regulates the Homeostasis of CD8+ T-Lymphocytes and Their Proliferation in Response to Antigen Stimulation"],"prefix":"10.3389","volume":"12","author":[{"given":"Zhilin","family":"Peng","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yiwen","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiancai","family":"Ma","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mo","family":"Zhou","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shiyu","family":"Wu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zheng","family":"Song","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yaochang","family":"Yuan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yingshi","family":"Chen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuzhuang","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Guanwen","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Feng","family":"Huang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yidan","family":"Qiao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Baijing","family":"Xia","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Weiwei","family":"Liu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jun","family":"Liu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xu","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xin","family":"He","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ting","family":"Pan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hanshi","family":"Xu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hui","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2021,8,26]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"98","DOI":"10.1111\/j.0105-2896.2005.00223.x","article-title":"Severe Combined Immunodeficiency. 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