Role of glycine N-methyltransferase in the regulation of T-cell responses in experimental autoimmune encephalomyelitis

Chung Hsien Li, Ming Hong Lin, Shih Han Chu, Pang Hsien Tu, Cheng Chieh Fang, Chia Hung Yen, Peir In Liang, Jason C. Huang, Yu Chia Su, Huey Kang Sytwu, Yi Ming A.rthur Chen

Research output: Contribution to journalArticle

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Abstract

Glycine N-methyltransferase (GNMT) is known for its function as a tumor suppressor gene. Since 100% of female Gnmt(-/-) mice developed hepatocellular carcinoma, we hypothesized that Gnmt(-/-) mice may have defective immune surveillance. In this study, we examined the immune modulation of GNMT in T-cell responses using experimental autoimmune encephalomyelitis (EAE). The results showed that EAE severity was reduced significantly in Gnmt(-/-) mice. Pathological examination of the spinal cords revealed that Gnmt(-/-) mice had significantly lower levels of mononuclear cell infiltration and demyelination than the wild-type mice. In addition, quantitative real-time PCR showed that expression levels of proinflammatory cytokines, including interferon (IFN)-γ and interleukin (IL)-17A, were much lower in the spinal cord of Gnmt(-/-) than in that of wild-type mice. Accordingly, myelin oligodendrocyte glycoprotein (MOG)-specific T-cell proliferation and induction of T-helper (Th)1 and Th17 cells were markedly suppressed in MOG(35-55)-induced Gnmt(-/-) mice. Moreover, the number of regulatory T (Treg) cells was increased significantly in these mice. When the T-cell receptor was stimulated, the proliferative capacity and the activation status of mTOR-associated downstream signaling were decreased significantly in Gnmt(-/-) CD4(+) T cells via an IL-2- and CD25-independent manner. Moreover, GNMT deficiency enhanced the differentiation of Treg cells without affecting the differentiation of Th1 and Th17 cells. Furthermore, the severity of EAE in mice adoptive transferred with GNMT-deficient CD4(+) T cells was much milder than in those with wild-type CD4(+) T cells. In summary, our findings suggest that GNMT is involved in the pathogenesis of EAE and plays a crucial role in the regulation of CD4(+) T-cell functions.

Original languageEnglish
Pages (from-to)684-696
Number of pages13
JournalMolecular medicine (Cambridge, Mass.)
Volume20
DOIs
Publication statusPublished - Jan 1 2014
Externally publishedYes

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Glycine N-Methyltransferase
Autoimmune Experimental Encephalomyelitis
T-Lymphocytes
Regulatory T-Lymphocytes
Th17 Cells
Th1 Cells
Spinal Cord
Myelin-Oligodendrocyte Glycoprotein
Interleukin-17
Demyelinating Diseases
T-Cell Antigen Receptor
Tumor Suppressor Genes
Interferons
Interleukin-2
Real-Time Polymerase Chain Reaction
Hepatocellular Carcinoma

ASJC Scopus subject areas

  • Molecular Medicine
  • Molecular Biology
  • Genetics
  • Genetics(clinical)

Cite this

Role of glycine N-methyltransferase in the regulation of T-cell responses in experimental autoimmune encephalomyelitis. / Li, Chung Hsien; Lin, Ming Hong; Chu, Shih Han; Tu, Pang Hsien; Fang, Cheng Chieh; Yen, Chia Hung; Liang, Peir In; Huang, Jason C.; Su, Yu Chia; Sytwu, Huey Kang; Chen, Yi Ming A.rthur.

In: Molecular medicine (Cambridge, Mass.), Vol. 20, 01.01.2014, p. 684-696.

Research output: Contribution to journalArticle

Li, Chung Hsien ; Lin, Ming Hong ; Chu, Shih Han ; Tu, Pang Hsien ; Fang, Cheng Chieh ; Yen, Chia Hung ; Liang, Peir In ; Huang, Jason C. ; Su, Yu Chia ; Sytwu, Huey Kang ; Chen, Yi Ming A.rthur. / Role of glycine N-methyltransferase in the regulation of T-cell responses in experimental autoimmune encephalomyelitis. In: Molecular medicine (Cambridge, Mass.). 2014 ; Vol. 20. pp. 684-696.
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AU - Yen, Chia Hung

AU - Liang, Peir In

AU - Huang, Jason C.

AU - Su, Yu Chia

AU - Sytwu, Huey Kang

AU - Chen, Yi Ming A.rthur

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