{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,24]],"date-time":"2026-10-24T00:20:40Z","timestamp":1792801240619,"version":"4.5.0"},"reference-count":46,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2025,6,2]],"date-time":"2025-06-02T00:00:00Z","timestamp":1748822400000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2025,6,2]],"date-time":"2025-06-02T00:00:00Z","timestamp":1748822400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"funder":[{"name":"Intramural Research program, NICHD, NIH.","award":["ZIA HD001310-35"],"award-info":[{"award-number":["ZIA HD001310-35"]}]},{"name":"Intramural Research program, NICHD, NIH.","award":["ZIA HD001310-35"],"award-info":[{"award-number":["ZIA HD001310-35"]}]},{"name":"Intramural Research program, NICHD, NIH.","award":["ZIA HD001310-35"],"award-info":[{"award-number":["ZIA HD001310-35"]}]},{"name":"Intramural Research program, NICHD, NIH.","award":["ZIA HD001310-35"],"award-info":[{"award-number":["ZIA HD001310-35"]}]},{"name":"Intramural Research program, NICHD, NIH.","award":["ZIA HD001310-35"],"award-info":[{"award-number":["ZIA HD001310-35"]}]},{"name":"Intramural Research program, NICHD, NIH.","award":["ZIA HD001310-35"],"award-info":[{"award-number":["ZIA HD001310-35"]}]},{"name":"Intramural Research program, NICHD, NIH.","award":["ZIA HD001310-35"],"award-info":[{"award-number":["ZIA HD001310-35"]}]},{"name":"Intramural Research program, NICHD, NIH.","award":["ZIA HD001310-35"],"award-info":[{"award-number":["ZIA HD001310-35"]}]},{"name":"Intramural Research program, NICHD, NIH.","award":["ZIA HD001310-35"],"award-info":[{"award-number":["ZIA HD001310-35"]}]},{"name":"Eunice Kennedy Shriver National Institute of Child Health and Human Development","id":[{"id":"https:\/\/ror.org\/04byxyr05","id-type":"ROR","asserted-by":"crossref"}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["J Neuroinflammation"],"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>\n                    Microglia are resident innate immune cells in the central nervous system (CNS) that provides anti-microbial protection but also promote neuroinflammation. BRD4 is a chromatin reader that binds to acetylated histones and directs transcription of numerous genes. However, it is unknown whether and how BRD4 regulates microglia function. We addressed the role of microglia and BRD4 in a neuroinflammatory disease, experimental autoimmune encephalomyelitis (EAE), a mouse model for multiple sclerosis. It was reported earlier that in EAE, upon initial T cell activation in the peripheral lymphoid organs, CD4\n                    <jats:sup>+<\/jats:sup>\n                    T cells migrate to CNS and are reactivated by resident or migratory antigen presenting cells resulting in full manifestation of EAE (Rossi and Constantin, Front Immunol 7:506, 2016), (Plastini et al., Front Cell Neurosci 14:269, 2020). Using conditional deletion of\n                    <jats:italic>Brd4<\/jats:italic>\n                    in CD4 T cells, we reveal that BRD4 regulates T helper cell differentiation and promotes T cell migration to CNS resulting in EAE. It remained unclear whether resident microglia are capable of reactivating migrating T cells to the CNS and if BRD4 plays a role in the process. To determine the role of microglial BRD4 in EAE, we constructed conditional knockout mice lacking\n                    <jats:italic>Brd4<\/jats:italic>\n                    (Brd4cKO) in microglia. RNA-seq analysis showed that\n                    <jats:italic>Brd4<\/jats:italic>\n                    deletion led to the downregulation of many microglia genes in both naive and EAE conditions. Consequently, Brd4cKO mice had markedly reduced EAE pathology, namely reduced paralysis, absence of axonal demyelination and inhibited expression of inflammatory cytokines. In vehicle treated mice (vehicle) abundant number of T cells were found to be near microglia that may lead to T cell- microglia interaction and T cell reactivation. In contrast, the number of T cells detected in the CNS of Brd4cKO mice was much fewer. This may lead to reduced T cell- microglia interaction, failure of T cells to get reactivated and hence failed to achieve full manifestation of EAE. These results demonstrate that microglia are critically involved in EAE disease progression for which BRD4 is essential. In summary, BRD4 directs transcription of genes defining microglia function. By so doing BRD4 promotes demyelination and neuroinflammation to exacerbate EAE.\n                  <\/jats:p>","DOI":"10.1186\/s12974-025-03449-9","type":"journal-article","created":{"date-parts":[[2025,6,2]],"date-time":"2025-06-02T10:04:31Z","timestamp":1748858671000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":9,"title":["Brd4 expression in CD4 T cells and in microglia promotes neuroinflammation in experimental autoimmune encephalomyelitis"],"prefix":"10.1186","volume":"22","author":[{"given":"Anup","family":"Dey","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Matthew","family":"Butcher","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anne","family":"Gegonne","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ryoji","family":"Yagi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Keita","family":"Saeki","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eunju","family":"Lee","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dinah S.","family":"Singer","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jinfang","family":"Zhu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Keiko","family":"Ozato","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2025,6,2]]},"reference":[{"issue":"9","key":"3449_CR1","doi-asserted-by":"publisher","first-page":"2869","DOI":"10.1111\/ene.15360","volume":"29","author":"H Lassmann","year":"2022","unstructured":"Lassmann H. The contribution of neuropathology to multiple sclerosis research. Eur J Neurol. 2022;29(9):2869\u201377.","journal-title":"Eur J Neurol"},{"issue":"2","key":"3449_CR2","doi-asserted-by":"publisher","first-page":"136","DOI":"10.1038\/nn.4475","volume":"20","author":"M Prinz","year":"2017","unstructured":"Prinz M, Priller J. The role of peripheral immune cells in the CNS in steady state and disease. Nat Neurosci. 2017;20(2):136\u201344.","journal-title":"Nat Neurosci"},{"issue":"1","key":"3449_CR3","doi-asserted-by":"publisher","first-page":"1114","DOI":"10.1038\/s42003-022-04081-6","volume":"5","author":"LM Healy","year":"2022","unstructured":"Healy LM, Zia S, Plemel JR. Towards a definition of microglia heterogeneity. Communications Biology. 2022;5(1):1114.","journal-title":"Communications Biology"},{"issue":"12","key":"3449_CR4","doi-asserted-by":"publisher","first-page":"1896","DOI":"10.1038\/nn.3554","volume":"16","author":"SE Hickman","year":"2013","unstructured":"Hickman SE, Kingery ND, Ohsumi TK, Borowsky ML. Wang L-c, Means TK, El Khoury J: The microglial sensome revealed by direct RNA sequencing. Nat Neurosci. 2013;16(12):1896\u2013905.","journal-title":"Nat Neurosci"},{"issue":"5","key":"3449_CR5","doi-asserted-by":"publisher","first-page":"1271","DOI":"10.1016\/j.celrep.2020.01.010","volume":"30","author":"T Masuda","year":"2020","unstructured":"Masuda T, Sankowski R, Staszewski O, Prinz M. Microglia Heterogeneity in the Single-Cell Era. Cell Rep. 2020;30(5):1271\u201381.","journal-title":"Cell Rep"},{"issue":"10","key":"3449_CR6","doi-asserted-by":"publisher","first-page":"622","DOI":"10.1038\/s41583-018-0057-5","volume":"19","author":"O Butovsky","year":"2018","unstructured":"Butovsky O, Weiner HL. Microglial signatures and their role in health and disease. Nat Rev Neurosci. 2018;19(10):622\u201335.","journal-title":"Nat Rev Neurosci"},{"issue":"11","key":"3449_CR7","doi-asserted-by":"publisher","first-page":"1618","DOI":"10.1038\/nn.3531","volume":"16","author":"T Goldmann","year":"2013","unstructured":"Goldmann T, Wieghofer P, M\u00fcller PF, Wolf Y, Varol D, Yona S, Brendecke SM, Kierdorf K, Staszewski O, Datta M, et al. A new type of microglia gene targeting shows TAK1 to be pivotal in CNS autoimmune inflammation. Nat Neurosci. 2013;16(11):1618\u201326.","journal-title":"Nat Neurosci"},{"issue":"2","key":"3449_CR8","doi-asserted-by":"publisher","first-page":"187","DOI":"10.1016\/j.immuni.2013.11.022","volume":"40","author":"Y Yoshida","year":"2014","unstructured":"Yoshida Y, Yoshimi R, Yoshii H, Kim D, Dey A, Xiong H, Munasinghe J, Yazawa I, O\u2019Donovan MJ, Maximova OA, et al. The transcription factor IRF8 activates integrin-mediated TGF-\u03b2 signaling and promotes neuroinflammation. Immunity. 2014;40(2):187\u201398.","journal-title":"Immunity"},{"issue":"8","key":"3449_CR9","doi-asserted-by":"publisher","first-page":"1533","DOI":"10.1084\/jem.20132477","volume":"211","author":"R Yamasaki","year":"2014","unstructured":"Yamasaki R, Lu H, Butovsky O, Ohno N, Rietsch AM, Cialic R, Wu PM, Doykan CE, Lin J, Cotleur AC, et al. Differential roles of microglia and monocytes in the inflamed central nervous system. J Exp Med. 2014;211(8):1533\u201349.","journal-title":"J Exp Med"},{"issue":"8","key":"3449_CR10","doi-asserted-by":"publisher","DOI":"10.15252\/emmm.201708743","volume":"10","author":"A Zabala","year":"2018","unstructured":"Zabala A, Vazquez-Villoldo N, Rissiek B, Gejo J, Martin A, Palomino A, Perez-Samart\u00edn A, Pulagam KR, Lukowiak M, Capetillo-Zarate E, et al. P2X4 receptor controls microglia activation and favors remyelination in autoimmune encephalitis. EMBO Mol Med. 2018;10(8): e8743.","journal-title":"EMBO Mol Med"},{"issue":"12","key":"3449_CR11","doi-asserted-by":"publisher","first-page":"1749","DOI":"10.1038\/s41590-022-01360-6","volume":"23","author":"Z Haimon","year":"2022","unstructured":"Haimon Z, Frumer GR, Kim JS, Trzebanski S, Haffner-Krausz R, Ben-Dor S, Porat Z, Muschaweckh A, Chappell-Maor L, Boura-Halfon S, et al. Cognate microglia-T cell interactions shape the functional regulatory T cell pool in experimental autoimmune encephalomyelitis pathology. Nat Immunol. 2022;23(12):1749\u201362.","journal-title":"Nat Immunol"},{"issue":"7953","key":"3449_CR12","doi-asserted-by":"publisher","first-page":"668","DOI":"10.1038\/s41586-023-05788-0","volume":"615","author":"X Chen","year":"2023","unstructured":"Chen X, Firulyova M, Manis M, Herz J, Smirnov I, Aladyeva E, Wang C, Bao X, Finn MB, Hu H, et al. Microglia-mediated T cell infiltration drives neurodegeneration in tauopathy. Nature. 2023;615(7953):668\u201377.","journal-title":"Nature"},{"issue":"1","key":"3449_CR13","doi-asserted-by":"publisher","first-page":"16","DOI":"10.1038\/s41419-023-05551-3","volume":"14","author":"A Montilla","year":"2023","unstructured":"Montilla A, Zabala A, Er-Lukowiak M, Rissiek B, Magnus T, Rodriguez-Iglesias N, Sierra A, Matute C, Domercq M. Microglia and meningeal macrophages depletion delays the onset of experimental autoimmune encephalomyelitis. Cell Death Dis. 2023;14(1):16.","journal-title":"Cell Death Dis"},{"issue":"11","key":"3449_CR14","doi-asserted-by":"publisher","first-page":"2181","DOI":"10.1084\/jem.20130376","volume":"210","author":"DA Mele","year":"2013","unstructured":"Mele DA, Salmeron A, Ghosh S, Huang HR, Bryant BM, Lora JM. BET bromodomain inhibition suppresses TH17-mediated pathology. J Exp Med. 2013;210(11):2181\u201390.","journal-title":"J Exp Med"},{"issue":"4","key":"3449_CR15","doi-asserted-by":"publisher","first-page":"523","DOI":"10.1016\/j.molcel.2005.06.027","volume":"19","author":"MK Jang","year":"2005","unstructured":"Jang MK, Mochizuki K, Zhou M, Jeong HS, Brady JN, Ozato K. The bromodomain protein Brd4 is a positive regulatory component of P-TEFb and stimulates RNA polymerase II-dependent transcription. Mol Cell. 2005;19(4):523\u201334.","journal-title":"Mol Cell"},{"issue":"12","key":"3449_CR16","doi-asserted-by":"publisher","first-page":"1047","DOI":"10.1038\/nsmb.2912","volume":"21","author":"T Kanno","year":"2014","unstructured":"Kanno T, Kanno Y, LeRoy G, Campos E, Sun HW, Brooks SR, Vahedi G, Heightman TD, Garcia BA, Reinberg D, et al. BRD4 assists elongation of both coding and enhancer RNAs by interacting with acetylated histones. Nat Struct Mol Biol. 2014;21(12):1047\u201357.","journal-title":"Nat Struct Mol Biol"},{"issue":"4","key":"3449_CR17","doi-asserted-by":"publisher","first-page":"535","DOI":"10.1016\/j.molcel.2005.06.029","volume":"19","author":"Z Yang","year":"2005","unstructured":"Yang Z, Yik JH, Chen R, He N, Jang MK, Ozato K, Zhou Q. Recruitment of P-TEFb for stimulation of transcriptional elongation by the bromodomain protein Brd4. Mol Cell. 2005;19(4):535\u201345.","journal-title":"Mol Cell"},{"issue":"17","key":"3449_CR18","doi-asserted-by":"publisher","first-page":"6537","DOI":"10.1128\/.20.17.6537-6549.2000","volume":"20","author":"A Dey","year":"2000","unstructured":"Dey A, Ellenberg J, Farina A, Coleman AE, Maruyama T, Sciortino S, Lippincott-Schwartz J, Ozato K. A bromodomain protein, MCAP, associates with mitotic chromosomes and affects G(2)-to-M transition. Mol Cell Biol. 2000;20(17):6537\u201349.","journal-title":"Mol Cell Biol"},{"issue":"5","key":"3449_CR19","doi-asserted-by":"publisher","first-page":"513","DOI":"10.1016\/j.modgep.2004.03.002","volume":"4","author":"E Shang","year":"2004","unstructured":"Shang E, Salazar G, Crowley TE, Wang X, Lopez RA, Wang X, Wolgemuth DJ. Identification of unique, differentiation stage-specific patterns of expression of the bromodomain-containing genes Brd2, Brd3, Brd4, and Brdt in the mouse testis. Gene Expr Patterns. 2004;4(5):513\u20139.","journal-title":"Gene Expr Patterns"},{"issue":"7","key":"3449_CR20","doi-asserted-by":"publisher","first-page":"470","DOI":"10.1089\/jir.2015.0179","volume":"36","author":"M Bachu","year":"2016","unstructured":"Bachu M, Dey A, Ozato K. Chromatin Landscape of the IRF Genes and Role of the Epigenetic Reader BRD4. J Interferon Cytokine Res. 2016;36(7):470\u20135.","journal-title":"J Interferon Cytokine Res"},{"issue":"2","key":"3449_CR21","doi-asserted-by":"publisher","first-page":"814","DOI":"10.1091\/mbc.e05-08-0729","volume":"17","author":"A Nishiyama","year":"2006","unstructured":"Nishiyama A, Dey A, Miyazaki J, Ozato K. Brd4 is required for recovery from antimicrotubule drug-induced mitotic arrest: preservation of acetylated chromatin. Mol Biol Cell. 2006;17(2):814\u201323.","journal-title":"Mol Biol Cell"},{"key":"3449_CR22","doi-asserted-by":"crossref","unstructured":"Wu T, Hou H, Dey A, Bachu M, Chen X, Wisniewski J, Kudoh F, Chen C, Chauhan S, Xiao H et al: Bromodomain protein BRD4 directs mitotic cell division of mouse fibroblasts by inhibiting DNA damage. iScience 2024, 27(7):109797.","DOI":"10.1016\/j.isci.2024.109797"},{"issue":"7","key":"3449_CR23","doi-asserted-by":"publisher","DOI":"10.15252\/embj.2018100293","volume":"38","author":"A Dey","year":"2019","unstructured":"Dey A, Yang W, Gegonne A, Nishiyama A, Pan R, Yagi R, Grinberg A, Finkelman FD, Pfeifer K, Zhu J, et al. BRD4 directs hematopoietic stem cell development and modulates macrophage inflammatory responses. EMBO J. 2019;38(7): e100293.","journal-title":"EMBO J"},{"issue":"36","key":"3449_CR24","doi-asserted-by":"publisher","first-page":"14532","DOI":"10.1073\/pnas.1212264109","volume":"109","author":"HS Bandukwala","year":"2012","unstructured":"Bandukwala HS, Gagnon J, Togher S, Greenbaum JA, Lamperti ED, Parr NJ, Molesworth AM, Smithers N, Lee K, Witherington J, et al. Selective inhibition of CD4+ T-cell cytokine production and autoimmunity by BET protein and c-Myc inhibitors. Proc Natl Acad Sci U S A. 2012;109(36):14532\u20137.","journal-title":"Proc Natl Acad Sci U S A"},{"key":"3449_CR25","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1016\/j.jaut.2017.12.007","volume":"87","author":"R Stadhouders","year":"2018","unstructured":"Stadhouders R, Lubberts E, Hendriks RW. A cellular and molecular view of T helper 17 cell plasticity in autoimmunity. J Autoimmun. 2018;87:1\u201315.","journal-title":"J Autoimmun"},{"issue":"1","key":"3449_CR26","doi-asserted-by":"publisher","first-page":"117","DOI":"10.4049\/jimmunol.169.1.117","volume":"169","author":"HH Hofstetter","year":"2002","unstructured":"Hofstetter HH, Shive CL, Forsthuber TG. Pertussis toxin modulates the immune response to neuroantigens injected in incomplete Freund\u2019s adjuvant: induction of Th1 cells and experimental autoimmune encephalomyelitis in the presence of high frequencies of Th2 cells. J Immunol. 2002;169(1):117\u201325.","journal-title":"J Immunol"},{"issue":"12","key":"3449_CR27","doi-asserted-by":"publisher","first-page":"704","DOI":"10.1038\/s41582-019-0253-6","volume":"15","author":"Y Dong","year":"2019","unstructured":"Dong Y, Yong VW. When encephalitogenic T cells collaborate with microglia in multiple sclerosis. Nat Rev Neurol. 2019;15(12):704\u201317.","journal-title":"Nat Rev Neurol"},{"key":"3449_CR28","doi-asserted-by":"publisher","first-page":"269","DOI":"10.3389\/fncel.2020.00269","volume":"14","author":"MJ Plastini","year":"2020","unstructured":"Plastini MJ, Desu HL, Brambilla R. Dynamic Responses of Microglia in Animal Models of Multiple Sclerosis. Front Cell Neurosci. 2020;14:269.","journal-title":"Front Cell Neurosci"},{"issue":"1","key":"3449_CR29","doi-asserted-by":"publisher","first-page":"34","DOI":"10.1038\/s41421-022-00377-3","volume":"8","author":"W Tan","year":"2022","unstructured":"Tan W. Su P-YP, Leff J, Gao X, Chen J, Guan AK, Kalyanasundaram G, Ma A, Guan Z: Distinct phases of adult microglia proliferation: a Myc-mediated early phase and a Tnfaip3-mediated late phase. Cell Discovery. 2022;8(1):34.","journal-title":"Cell Discovery"},{"key":"3449_CR30","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2022.997786","volume":"13","author":"A Vidal-Itriago","year":"2022","unstructured":"Vidal-Itriago A, Radford RAW, Aramideh JA, Maurel C, Scherer NM, Don EK, Lee A, Chung RS, Graeber MB, Morsch M. Microglia morphophysiological diversity and its implications for the CNS. Front Immunol. 2022;13: 997786.","journal-title":"Front Immunol"},{"key":"3449_CR31","doi-asserted-by":"publisher","first-page":"430","DOI":"10.3389\/fimmu.2020.00430","volume":"11","author":"A Benmamar-Badel","year":"2020","unstructured":"Benmamar-Badel A, Owens T, Wlodarczyk A. Protective Microglial Subset in Development, Aging, and Disease: Lessons From Transcriptomic Studies. Front Immunol. 2020;11:430.","journal-title":"Front Immunol"},{"key":"3449_CR32","doi-asserted-by":"publisher","first-page":"90","DOI":"10.1016\/j.jneuroim.2018.09.002","volume":"324","author":"KM Garner","year":"2018","unstructured":"Garner KM, Amin R, Johnson RW, Scarlett EJ, Burton MD. Microglia priming by interleukin-6 signaling is enhanced in aged mice. J Neuroimmunol. 2018;324:90\u20139.","journal-title":"J Neuroimmunol"},{"issue":"1","key":"3449_CR33","doi-asserted-by":"publisher","first-page":"366","DOI":"10.1186\/s12974-020-02019-5","volume":"17","author":"P Honarpisheh","year":"2020","unstructured":"Honarpisheh P, Lee J, Banerjee A, Blasco-Conesa MP, Honarpisheh P, d\u2019Aigle J, Mamun AA, Ritzel RM, Chauhan A, Ganesh BP, et al. Potential caveats of putative microglia-specific markers for assessment of age-related cerebrovascular neuroinflammation. J Neuroinflammation. 2020;17(1):366.","journal-title":"J Neuroinflammation"},{"issue":"1","key":"3449_CR34","doi-asserted-by":"publisher","first-page":"117","DOI":"10.1016\/j.celrep.2018.06.007","volume":"24","author":"A Gegonne","year":"2018","unstructured":"Gegonne A, Chen Q-R, Dey A, Etzensperger R, Tai X, Singer A, Meerzaman D, Ozato K, Singer DS. Immature CD8 Single-Positive Thymocytes Are a Molecularly Distinct Subpopulation, Selectively Dependent on BRD4 for Their Differentiation. Cell Rep. 2018;24(1):117\u201329.","journal-title":"Cell Rep"},{"issue":"10","key":"3449_CR35","doi-asserted-by":"publisher","DOI":"10.15252\/embr.202357032","volume":"24","author":"H Yang","year":"2023","unstructured":"Yang H, Sui P, Guo Y, Chen S, Maloof ME, Ge G, Nihozeko F, Delma CR, Zhu G, Zhang P, et al. Loss of BRD4 induces cell senescence in HSC\/HPCs by deregulating histone H3 clipping. EMBO Rep. 2023;24(10): e57032.","journal-title":"EMBO Rep"},{"issue":"12","key":"3449_CR36","doi-asserted-by":"publisher","first-page":"5848","DOI":"10.4049\/jimmunol.1300771","volume":"191","author":"RA Sosa","year":"2013","unstructured":"Sosa RA, Murphey C, Ji N, Cardona AE, Forsthuber TG. The kinetics of myelin antigen uptake by myeloid cells in the central nervous system during experimental autoimmune encephalomyelitis. J Immunol. 2013;191(12):5848\u201357.","journal-title":"J Immunol"},{"issue":"8","key":"3449_CR37","doi-asserted-by":"publisher","first-page":"1308","DOI":"10.1002\/eji.201847540","volume":"48","author":"Y Wolf","year":"2018","unstructured":"Wolf Y, Shemer A, Levy-Efrati L, Gross M, Kim JS, Engel A, David E, Chappell-Maor L, Grozovski J, Rotkopf R, et al. Microglial MHC class II is dispensable for experimental autoimmune encephalomyelitis and cuprizone-induced demyelination. Eur J Immunol. 2018;48(8):1308\u201318.","journal-title":"Eur J Immunol"},{"issue":"3","key":"3449_CR38","doi-asserted-by":"publisher","first-page":"1402","DOI":"10.4049\/jimmunol.176.3.1402","volume":"176","author":"ED Ponomarev","year":"2006","unstructured":"Ponomarev ED, Shriver LP, Dittel BN. CD40 expression by microglial cells is required for their completion of a two-step activation process during central nervous system autoimmune inflammation. J Immunol. 2006;176(3):1402\u201310.","journal-title":"J Immunol"},{"issue":"3","key":"3449_CR39","doi-asserted-by":"publisher","first-page":"604","DOI":"10.1172\/JCI119571","volume":"100","author":"S Chabot","year":"1997","unstructured":"Chabot S, Williams G, Yong VW. Microglial production of TNF-alpha is induced by activated T lymphocytes. Involvement of VLA-4 and inhibition by interferonbeta-1b. J Clin Invest. 1997;100(3):604\u201312.","journal-title":"J Clin Invest"},{"issue":"19","key":"3449_CR40","doi-asserted-by":"publisher","first-page":"1619","DOI":"10.1182\/blood.2019001234","volume":"134","author":"T Ling","year":"2019","unstructured":"Ling T, Birger Y, Stankiewicz MJ, Ben-Haim N, Kalisky T, Rein A, Kugler E, Chen W, Fu C, Zhang K, et al. Chromatin occupancy and epigenetic analysis reveal new insights into the function of the GATA1 N terminus in erythropoiesis. Blood. 2019;134(19):1619\u201331.","journal-title":"Blood"},{"key":"3449_CR41","doi-asserted-by":"crossref","unstructured":"Jahagirdar R, Attwell S, Marusic S, Bendele A, Shenoy N, McLure KG, Gilham D, Norek K, Hansen HC, Yu R et al: RVX-297, a BET bromodomain inhibitor, has therapeutic effects in preclinical models of acute inflammation and autoimmune disease. Molecular Pharmacology 2017:mol.117.110379.","DOI":"10.1124\/mol.117.110379"},{"issue":"7327","key":"3449_CR42","doi-asserted-by":"publisher","first-page":"1119","DOI":"10.1038\/nature09589","volume":"468","author":"E Nicodeme","year":"2010","unstructured":"Nicodeme E, Jeffrey KL, Schaefer U, Beinke S, Dewell S, Chung CW, Chandwani R, Marazzi I, Wilson P, Coste H, et al. Suppression of inflammation by a synthetic histone mimic. Nature. 2010;468(7327):1119\u201323.","journal-title":"Nature"},{"issue":"4","key":"3449_CR43","doi-asserted-by":"publisher","first-page":"465","DOI":"10.1002\/ana.22054","volume":"68","author":"G Androdias","year":"2010","unstructured":"Androdias G, Reynolds R, Chanal M, Ritleng C, Confavreux C, Nataf S. Meningeal T cells associate with diffuse axonal loss in multiple sclerosis spinal cords. Ann Neurol. 2010;68(4):465\u201376.","journal-title":"Ann Neurol"},{"issue":"Pt 10","key":"3449_CR44","doi-asserted-by":"publisher","first-page":"2202","DOI":"10.1093\/brain\/awf235","volume":"125","author":"T Kuhlmann","year":"2002","unstructured":"Kuhlmann T, Lingfeld G, Bitsch A, Schuchardt J, Br\u00fcck W. Acute axonal damage in multiple sclerosis is most extensive in early disease stages and decreases over time. Brain. 2002;125(Pt 10):2202\u201312.","journal-title":"Brain"},{"issue":"2","key":"3449_CR45","doi-asserted-by":"publisher","first-page":"146","DOI":"10.1038\/nm1177","volume":"11","author":"FL Heppner","year":"2005","unstructured":"Heppner FL, Greter M, Marino D, Falsig J, Raivich G, H\u00f6velmeyer N, Waisman A, R\u00fclicke T, Prinz M, Priller J, et al. Experimental autoimmune encephalomyelitis repressed by microglial paralysis. Nat Med. 2005;11(2):146\u201352.","journal-title":"Nat Med"},{"issue":"4","key":"3449_CR46","doi-asserted-by":"publisher","first-page":"549","DOI":"10.1007\/s00401-020-02187-x","volume":"140","author":"J Hauptmann","year":"2020","unstructured":"Hauptmann J, Johann L, Marini F, Kitic M, Colombo E, Mufazalov IA, Krueger M, Karram K, Moos S, Wanke F, et al. Interleukin-1 promotes autoimmune neuroinflammation by suppressing endothelial heme oxygenase-1 at the blood-brain barrier. Acta Neuropathol. 2020;140(4):549\u201367.","journal-title":"Acta Neuropathol"}],"container-title":["Journal of Neuroinflammation"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1186\/s12974-025-03449-9.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/article\/10.1186\/s12974-025-03449-9\/fulltext.html","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1186\/s12974-025-03449-9.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,6,2]],"date-time":"2025-06-02T11:02:52Z","timestamp":1748862172000},"score":1,"resource":{"primary":{"URL":"https:\/\/jneuroinflammation.biomedcentral.com\/articles\/10.1186\/s12974-025-03449-9"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,6,2]]},"references-count":46,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2025,12]]}},"alternative-id":["3449"],"URL":"https:\/\/doi.org\/10.1186\/s12974-025-03449-9","relation":{"has-preprint":[{"id-type":"doi","id":"10.21203\/rs.3.rs-5271234\/v1","asserted-by":"object"}]},"ISSN":["1742-2094"],"issn-type":[{"value":"1742-2094","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,6,2]]},"assertion":[{"value":"15 October 2024","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"17 April 2025","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"2 June 2025","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Declarations"}},{"value":"All animal studies were approved by National Institute of Child Health and Human development (Animal study Protocol #20\u2013044, #23\u2013044) and was carried out in compliance with National Institute of Health guideline.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethics approval and consent to participate"}},{"value":"The authors declare no competing interests.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"148"}}