4.7 Article

AMIGO2 modulates T cell functions and its deficiency in mice ameliorates experimental autoimmune encephalomyelitis

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

  1. Academy of Finland [256107, 283085, 259581, 265179, 292725]
  2. Centre of Excellence in Molecular Systems Immunology and Physiology Research [250114]
  3. Magnus Ehrnrooth Foundation
  4. Sigrid Juselius Foundation
  5. Doctoral Programme in Biomedicine at the University of Helsinki
  6. China Scholarship Council
  7. Finnish MS Foundation
  8. Turku Doctoral Programme of Molecular Medicine
  9. Ida Montinin Foundation
  10. Academy of Finland (AKA) [256107, 259581, 265179, 283085, 292725, 259581, 265179, 283085, 256107, 292725] Funding Source: Academy of Finland (AKA)

向作者/读者索取更多资源

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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