期刊
BRAIN BEHAVIOR AND IMMUNITY
卷 62, 期 -, 页码 110-123出版社
ACADEMIC PRESS INC ELSEVIER SCIENCE
DOI: 10.1016/j.bbi.2017.01.009
关键词
AMIGO2; EAE; MS; T-bet; GATA-3; Akt; NF-kB; NFAT1; GSK-3 beta
资金
- Academy of Finland [256107, 283085, 259581, 265179, 292725]
- Centre of Excellence in Molecular Systems Immunology and Physiology Research [250114]
- Magnus Ehrnrooth Foundation
- Sigrid Juselius Foundation
- Doctoral Programme in Biomedicine at the University of Helsinki
- China Scholarship Council
- Finnish MS Foundation
- Turku Doctoral Programme of Molecular Medicine
- Ida Montinin Foundation
- Academy of Finland (AKA) [256107, 259581, 265179, 283085, 292725, 259581, 265179, 283085, 256107, 292725] Funding Source: Academy of Finland (AKA)
The immune function of AMIGO2 is currently unknown. Here, we revealed novel roles of AMIGO2 in modulating T-cell functions and EAE using Amigo2-knockout (AMG2K0) mice. Amigo2 was abundantly expressed by murine T helper (Th) cells. Its deficiency impaired transplanted T-cell infiltration into the secondary lymphoid organs and dampened Th-cell activation, but promoted splenic Th-cell proliferation and abundancy therein. AMG2K0 Th cells had respectively elevated T-bet in Th1- and GATA-3 in Th2-lineage during early Th-cell differentiation, accompanied with increased IFN-gamma and IL-10 but decreased IL-17A production. AMG2K0 mice exhibited ameliorated EAE, dampened spinal T-cell accumulation, decreased serum IL-17A levels and enhanced splenic IL-10 production. Adoptive transfer of encephalitogenic AMG2K0 T cells induced milder EAE and dampened spinal Th-cell accumulation and Tnf expression. Mechanistically, Amigo2-overexpression in 293T cells dampened NF-kB transcriptional activity, while Amigo2-deficiency enhanced Akt but suppressed GSK-3 beta phosphorylation and promoted nuclear translocations of NF-kB and NFAT1 in Th-cells. Collectively, our data demonstrate that AMIGO2 is important in regulating T-cell functions and EAE, and may be harnessed as a potential therapeutic target for multiple sclerosis. (C) 2017 Elsevier Inc. All rights reserved.
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