title: AMIGO2 modulates T cell functions and its deficiency in mice ameliorates experimental autoimmune encephalomyelitis.
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.
authors.affiliation: Neuroscience Center, Helsinki Institute of Life Science (HiLIFE), University of Helsinki, Helsinki, Finland. Electronic address: zhilin.li@helsinki.fi.
authors.forename: Zhilin
authors.initials: Z
authors.lastname: Li
authors.affiliation: Turku Centre for Biotechnology, University of Turku and Åbo Akademi University, Turku, Finland. Electronic address: mkhan@btk.fi.
authors.forename: Mohd Moin
authors.initials: MM
authors.lastname: Khan
authors.affiliation: Neuroscience Center, Helsinki Institute of Life Science (HiLIFE), University of Helsinki, Helsinki, Finland. Electronic address: juha.kuja-panula@helsinki.fi.
authors.forename: Juha
authors.initials: J
authors.lastname: Kuja-Panula
authors.affiliation: College of Life Sciences, Wuhan University, Wuhan, China. Electronic address: 1328492097@qq.com.
authors.forename: Hongyun
authors.initials: H
authors.lastname: Wang
authors.affiliation: College of Life Sciences, Wuhan University, Wuhan, China. Electronic address: chenyu@whu.edu.cn.
authors.forename: Yu
authors.initials: Y
authors.lastname: Chen
authors.affiliation: College of Life Sciences, Wuhan University, Wuhan, China; School of Basic Medical Sciences, Wuhan University, Wuhan, China. Electronic address: dguo@whu.edu.cn.
authors.forename: Deyin
authors.initials: D
authors.lastname: Guo
authors.affiliation: Turku Centre for Biotechnology, University of Turku and Åbo Akademi University, Turku, Finland. Electronic address: zchen@btk.fi.
authors.forename: Zhi Jane
authors.initials: ZJ
authors.lastname: Chen
authors.affiliation: Turku Centre for Biotechnology, University of Turku and Åbo Akademi University, Turku, Finland. Electronic address: riitta.lahesmaa@btk.fi.
authors.forename: Riitta
authors.initials: R
authors.lastname: Lahesmaa
authors.affiliation: Neuroscience Center, Helsinki Institute of Life Science (HiLIFE), University of Helsinki, Helsinki, Finland. Electronic address: heikki.rauvala@helsinki.fi.
authors.forename: Heikki
authors.initials: H
authors.lastname: Rauvala
authors.affiliation: 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.
authors.forename: Li
authors.initials: L
authors.lastname: Tian
mesh_terms: D019264:Adoptive Transfer; D000818:Animals; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D020381:Interleukin-17 / Q000097:blood; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D018345:Mice, Knockout; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000378:metabolism*; D013154:Spleen / Q000276:immunology / Q000378:metabolism*; D018417:Th1 Cells / Q000276:immunology / Q000378:metabolism*; D058504:Th17 Cells / Q000276:immunology / Q000378:metabolism*
chemical_list: C476133:Amigo2 protein, mouse; C098680:Il17a protein, mouse; D020381:Interleukin-17; D008565:Membrane Proteins; D009419:Nerve Tissue Proteins
keywords: AMIGO2; Akt; EAE; GATA-3; GSK-3β; MS; NF-kB; NFAT1; T-bet