1. T cell-specific BLIMP-1 deficiency exacerbates experimental autoimmune encephalomyelitis in nonobese diabetic mice by increasing Th1 and Th17 cells.
- Author
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Lin MH, Yeh LT, Chen SJ, Chiou HY, Chu CC, Yen LB, Lin KI, Chang DM, and Sytwu HK
- Subjects
- Adoptive Transfer, Animals, Brain metabolism, Brain pathology, CD4-Positive T-Lymphocytes, Cells, Cultured, Encephalomyelitis, Autoimmune, Experimental genetics, Encephalomyelitis, Autoimmune, Experimental metabolism, Mice, Mice, Inbred NOD, Mice, Knockout, Positive Regulatory Domain I-Binding Factor 1, STAT3 Transcription Factor genetics, STAT3 Transcription Factor metabolism, STAT4 Transcription Factor genetics, STAT4 Transcription Factor metabolism, Specific Pathogen-Free Organisms, Spinal Cord metabolism, Spinal Cord pathology, Transcription Factors genetics, Encephalomyelitis, Autoimmune, Experimental immunology, Gene Expression Regulation immunology, Th1 Cells physiology, Th17 Cells physiology, Transcription Factors metabolism
- 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., (Copyright © 2014 Elsevier Inc. All rights reserved.)
- Published
- 2014
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