{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,18]],"date-time":"2026-05-18T22:17:01Z","timestamp":1779142621780,"version":"3.51.4"},"reference-count":48,"publisher":"American Society for Clinical Investigation","issue":"23","license":[{"start":{"date-parts":[[2022,12,8]],"date-time":"2022-12-08T00:00:00Z","timestamp":1670457600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"crossref","award":["R01AI129906"],"award-info":[{"award-number":["R01AI129906"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2022,12,8]]},"abstract":"<jats:p>\n                    BRD4 is a bromodomain extraterminal domain family member and functions primarily as a chromatin reader regulating genes involved in cell-fate decisions. Here, we bred\n                    <jats:italic>\n                      Brd4\n                      <jats:sup>fl\/fl<\/jats:sup>\n                      Ox40-Cre\n                    <\/jats:italic>\n                    mice in which\n                    <jats:italic>Brd4<\/jats:italic>\n                    was conditionally deleted in OX40-expressing cells to examine the role of BRD4 in regulating immune responses. We found that the\n                    <jats:italic>\n                      Brd4\n                      <jats:sup>fl\/fl<\/jats:sup>\n                      Ox40-Cre\n                    <\/jats:italic>\n                    mice developed profound alopecia and dermatitis, while other organs and tissues were not affected. Surprisingly, lineage-tracing experiments using the\n                    <jats:italic>\n                      Rosa26\n                      <jats:sup>fl\/fl<\/jats:sup>\n                      -Yfp\n                    <\/jats:italic>\n                    mice identified a subset of hair follicle stem cells (HFSCs) that constitutively express OX40, and deletion of\n                    <jats:italic>Brd4<\/jats:italic>\n                    specifically in such HFSCs resulted in cell death and a complete loss of skin hair growth. We also found that death of HFSCs triggered massive activation of the intradermal \u03b3\u03b4 T cells, which induced epidermal hyperplasia and dermatitis by producing the inflammatory cytokine IL-17. Interestingly, deletion of\n                    <jats:italic>Brd4<\/jats:italic>\n                    in Foxp3\n                    <jats:sup>+<\/jats:sup>\n                    Tregs, which also constitutively express OX40, compromised their suppressive functions, and this, in turn, contributed to the enhanced activation of \u03b3\u03b4 T cells, as well as the severity of dermatitis and hair follicle destruction. Thus, our data demonstrate an unexpected role of BRD4 in regulating skin follicle stem cells and skin inflammation.\n                  <\/jats:p>","DOI":"10.1172\/jci.insight.164534","type":"journal-article","created":{"date-parts":[[2022,10,18]],"date-time":"2022-10-18T12:00:48Z","timestamp":1666094448000},"source":"Crossref","is-referenced-by-count":4,"title":["Ox40-Cre\u2013mediated deletion of BRD4 reveals an unexpected phenotype of hair follicle stem cells in alopecia"],"prefix":"10.1172","volume":"7","author":[{"given":"Mou","family":"Wen","sequence":"first","affiliation":[{"name":"Immunobiology and Transplant Science Center and Department of Surgery, Houston Methodist Hospital, Texas Medical Center, Houston, Texas, USA."},{"name":"Department of Thoracic Surgery, the Second Xiangya Hospital, Central South University, Changsha, China."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yuanlin","family":"Ying","sequence":"additional","affiliation":[{"name":"Immunobiology and Transplant Science Center and Department of Surgery, Houston Methodist Hospital, Texas Medical Center, Houston, Texas, USA."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6644-6118","authenticated-orcid":true,"given":"Xiang","family":"Xiao","sequence":"additional","affiliation":[{"name":"Immunobiology and Transplant Science Center and Department of Surgery, Houston Methodist Hospital, Texas Medical Center, Houston, Texas, USA."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5610-7307","authenticated-orcid":true,"given":"Preston R.","family":"Arnold","sequence":"additional","affiliation":[{"name":"Immunobiology and Transplant Science Center and Department of Surgery, Houston Methodist Hospital, Texas Medical Center, Houston, Texas, USA."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Guangchuan","family":"Wang","sequence":"additional","affiliation":[{"name":"Immunobiology and Transplant Science Center and Department of Surgery, Houston Methodist Hospital, Texas Medical Center, Houston, Texas, USA."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xiufeng","family":"Chu","sequence":"additional","affiliation":[{"name":"Immunobiology and Transplant Science Center and Department of Surgery, Houston Methodist Hospital, Texas Medical Center, Houston, Texas, USA."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Rafik M.","family":"Ghobrial","sequence":"additional","affiliation":[{"name":"Immunobiology and Transplant Science Center and Department of Surgery, Houston Methodist Hospital, Texas Medical Center, Houston, Texas, USA."},{"name":"Department of Surgery, Weill Cornell Medical College of Cornell University, New York, New York, USA."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5981-2762","authenticated-orcid":true,"given":"Xian C.","family":"Li","sequence":"additional","affiliation":[{"name":"Immunobiology and Transplant Science Center and Department of Surgery, Houston Methodist Hospital, Texas Medical Center, Houston, Texas, USA."},{"name":"Department of Surgery, Weill Cornell Medical College of Cornell University, New York, New York, 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