title: T cell-specific BLIMP-1 deficiency exacerbates experimental autoimmune encephalomyelitis in nonobese diabetic mice by increasing Th1 and Th17 cells.
abstract: Recently, we demonstrated that B lymphocyte-induced maturation protein 1 (BLIMP-1) has a role in regulating the differentiation and effector function of Th1 and Th17 cells. As these cells play critical roles in the induction and pathogenesis of experimental autoimmune encephalomyelitis (EAE), we investigated the potential role of T cell BLIMP-1 in modulating MOG35-55-induced EAE. We established T cell-specific BLIMP-1 conditional knockout (CKO) NOD mice to dissect the role of BLIMP-1 in EAE using loss-of-function model. Our results indicate that EAE severity is dramatically exacerbated in CKO mice. The numbers of CNS-infiltrating Th1, Th17, IFN-γ(+)IL-17A(+), and IL-21(+)IL-17A(+) CD4(+) T cells are remarkably increased in brain and spinal cord of CKO mice. Moreover, the ratio of Tregs/effectors and IL-10 production of Tregs are significantly downregulated in CNS of CKO mice. We conclude that BLIMP-1 suppresses autoimmune encephalomyelitis via downregulating Th1 and Th17 cells and impairing Treg cells.
authors.affiliation: Department and Graduate Institute of Microbiology and Immunology, National Defense Medical Center, Taipei, Taiwan, ROC.
authors.forename: Ming-Hong
authors.initials: MH
authors.lastname: Lin
authors.affiliation: Department and Graduate Institute of Microbiology and Immunology, National Defense Medical Center, Taipei, Taiwan, ROC.
authors.forename: Li-Tzu
authors.initials: LT
authors.lastname: Yeh
authors.affiliation: Department of Pediatrics, Tri-Service General Hospital, National Defense Medical Center, Taipei, Taiwan, ROC.
authors.forename: Shyi-Jou
authors.initials: SJ
authors.lastname: Chen
authors.affiliation: Graduate Institute of Life Sciences, National Defense Medical Center, Taipei, Taiwan, ROC.
authors.forename: Hsin-Ying C
authors.initials: HY
authors.lastname: Chiou
authors.affiliation: Department of Anesthesiology, Chi Mei Medical Center, Tainan, Taiwan, ROC; Department of Recreation and Health-Care Management, Chia Nan University of Pharmacy and Science, Tainan, Taiwan, ROC. Electronic address: chinchen.chu@gmail.com.
authors.forename: Chin-Chen
authors.initials: CC
authors.lastname: Chu
authors.affiliation: Institute of Cellular and System Medicine, National Health Research Institutes, Zhunan, Taiwan, ROC.
authors.forename: Linju B
authors.initials: LB
authors.lastname: Yen
authors.affiliation: Genomics Research Center, Academia Sinica, Taipei, Taiwan, ROC.
authors.forename: Kuo-I
authors.initials: KI
authors.lastname: Lin
authors.affiliation: Department of Internal Medicine, Tri-Service General Hospital, National Defense Medical Center, Taipei, Taiwan, ROC.
authors.forename: Deh-Ming
authors.initials: DM
authors.lastname: Chang
authors.affiliation: Department and Graduate Institute of Microbiology and Immunology, National Defense Medical Center, Taipei, Taiwan, ROC; Graduate Institute of Life Sciences, National Defense Medical Center, Taipei, Taiwan, ROC. Electronic address: sytwu@ndmctsgh.edu.tw.
authors.forename: Huey-Kang
authors.initials: HK
authors.lastname: Sytwu
mesh_terms: D019264:Adoptive Transfer; D000818:Animals; D001921:Brain / Q000378:metabolism / Q000473:pathology; D015496:CD4-Positive T-Lymphocytes; D002478:Cells, Cultured; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D005786:Gene Expression Regulation / Q000276:immunology*; D051379:Mice; D016688:Mice, Inbred NOD; D018345:Mice, Knockout; D000074462:Positive Regulatory Domain I-Binding Factor 1; D050796:STAT3 Transcription Factor / Q000235:genetics / Q000378:metabolism; D050797:STAT4 Transcription Factor / Q000235:genetics / Q000378:metabolism; D013047:Specific Pathogen-Free Organisms; D013116:Spinal Cord / Q000378:metabolism / Q000473:pathology; D018417:Th1 Cells / Q000502:physiology*; D058504:Th17 Cells / Q000502:physiology*; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism*
chemical_list: C513258:Prdm1 protein, mouse; D050796:STAT3 Transcription Factor; D050797:STAT4 Transcription Factor; C494087:Stat3 protein, mouse; C494091:Stat4 protein, mouse; D014157:Transcription Factors; D000074462:Positive Regulatory Domain I-Binding Factor 1
keywords: BLIMP-1; EAE; IL-10; Th1; Th17; Treg