Format

Send to

Choose Destination
Brain Behav Immun. 2017 May;62:110-123. doi: 10.1016/j.bbi.2017.01.009. Epub 2017 Feb 1.

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

Author information

1
Neuroscience Center, Helsinki Institute of Life Science (HiLIFE), University of Helsinki, Helsinki, Finland. Electronic address: zhilin.li@helsinki.fi.
2
Turku Centre for Biotechnology, University of Turku and Åbo Akademi University, Turku, Finland. Electronic address: mkhan@btk.fi.
3
Neuroscience Center, Helsinki Institute of Life Science (HiLIFE), University of Helsinki, Helsinki, Finland. Electronic address: juha.kuja-panula@helsinki.fi.
4
College of Life Sciences, Wuhan University, Wuhan, China. Electronic address: 1328492097@qq.com.
5
College of Life Sciences, Wuhan University, Wuhan, China. Electronic address: chenyu@whu.edu.cn.
6
College of Life Sciences, Wuhan University, Wuhan, China; School of Basic Medical Sciences, Wuhan University, Wuhan, China. Electronic address: dguo@whu.edu.cn.
7
Turku Centre for Biotechnology, University of Turku and Åbo Akademi University, Turku, Finland. Electronic address: zchen@btk.fi.
8
Turku Centre for Biotechnology, University of Turku and Åbo Akademi University, Turku, Finland. Electronic address: riitta.lahesmaa@btk.fi.
9
Neuroscience Center, Helsinki Institute of Life Science (HiLIFE), University of Helsinki, Helsinki, Finland. Electronic address: heikki.rauvala@helsinki.fi.
10
Neuroscience Center, Helsinki Institute of Life Science (HiLIFE), University of Helsinki, Helsinki, Finland; Psychiatry Research Center, Beijing Huilongguan Hospital, Peking University, Beijing, China. Electronic address: li.tian@helsinki.fi.

Abstract

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 (AMG2KO) 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. AMG2KO Th cells had respectively elevated T-bet in Th1- and GATA-3 in Th2-lineage during early Th-cell differentiation, accompanied with increased IFN-γ and IL-10 but decreased IL-17A production. AMG2KO mice exhibited ameliorated EAE, dampened spinal T-cell accumulation, decreased serum IL-17A levels and enhanced splenic IL-10 production. Adoptive transfer of encephalitogenic AMG2KO 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-3β 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.

KEYWORDS:

AMIGO2; Akt; EAE; GATA-3; GSK-3β; MS; NF-kB; NFAT1; T-bet

PMID:
28119027
DOI:
10.1016/j.bbi.2017.01.009
[Indexed for MEDLINE]

Supplemental Content

Full text links

Icon for Elsevier Science
Loading ...
Support Center