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AMIGO2 modulates T cell functions and its deficiency in mice ameliorates experimental autoimmune encephalomyelitis
Tekijät: Zhilin Li, Mohd Moin Khan, Juha Kuja-Panula, Hongyun Wang, Yu Chen, Deyin Guo, Zhi Jane Chen, Riitta Lahesmaa, Heikki Rauvala, Li Tian,
Kustantaja: ACADEMIC PRESS INC ELSEVIER SCIENCE
Julkaisuvuosi: 2017
Journal: Brain, Behavior, and Immunity
Tietokannassa oleva lehden nimi: BRAIN BEHAVIOR AND IMMUNITY
Lehden akronyymi: BRAIN BEHAV IMMUN
Vuosikerta: 62
Aloitussivu: 110
Lopetussivu: 123
Sivujen määrä: 14
ISSN: 0889-1591
DOI: https://doi.org/10.1016/j.bbi.2017.01.009
Tiivistelmä
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.
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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