In:
Cancer Research, American Association for Cancer Research (AACR), Vol. 75, No. 15_Supplement ( 2015-08-01), p. 1295-1295
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 significantly reduced in Gnmt−/− mice. Pathological examination of the spinal cords revealed that Gnmt−/- mice had significantly lower level of mononuclear cell infiltration and demyelination than the wild-type mice. In addition, quantitative real-time PCR showed that expression levels of pro-inflammatory cytokines, including IFN-gamma and 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 MOG35-55 induced Gnmt−/- mice. Moreover, the amount of regulatory T cells was significantly increased in these mice. When the T cell receptor was stimulated, the proliferative capacity and the activation status of mTOR-associated downstream signaling were significantly decreased in GNMT−/- CD4+ T cells via an IL-2 and CD25-independent manner. Moreover, GNMT deficiency enhanced the differentiation of regulatory T 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. Citation Format: Chung-Hsien Li, Ming-Hong Lin, Yen-Fu Chen, 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. Chen. Role of glycine N-methyltransferase in the regulation of T cell responses in experimental autoimmune encephalomyelitis. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 1295. doi:10.1158/1538-7445.AM2015-1295
Type of Medium:
Online Resource
ISSN:
0008-5472
,
1538-7445
DOI:
10.1158/1538-7445.AM2015-1295
Language:
English
Publisher:
American Association for Cancer Research (AACR)
Publication Date:
2015
detail.hit.zdb_id:
2036785-5
detail.hit.zdb_id:
1432-1
detail.hit.zdb_id:
410466-3
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