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

Authors: Li, Zhilin  Khan, Mohd Moin  Kuja-Panula, Juha  Wang, Hongyun  Chen, Yu  Guo, Deyin  Chen, Zhi Jane  Lahesmaa, Riitta  Rauvala, Heikki  Tian, Li 
Citation: Li Z, etal., Brain Behav Immun. 2017 May;62:110-123. doi: 10.1016/j.bbi.2017.01.009. Epub 2017 Feb 1.
Pubmed: (View Article at PubMed) PMID:28119027
DOI: Full-text: DOI:10.1016/j.bbi.2017.01.009

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.


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CRRD Object Information
CRRD ID: 14392778
Created: 2019-02-27
Species: All species
Last Modified: 2019-02-27
Status: ACTIVE


RGD is funded by grant HL64541 from the National Heart, Lung, and Blood Institute on behalf of the NIH.