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  • Ablation of core fucosylation attenuates the signal transduction via T cell receptor to suppress the T cell development.

Ablation of core fucosylation attenuates the signal transduction via T cell receptor to suppress the T cell development.

Molecular immunology (2019-06-24)
Wei Liang, Shanshan Mao, Ming Li, Nianzhu Zhang, Shijie Sun, Hui Fang, Jianing Zhang, Jianguo Gu, Jingyu Wang, Wenzhe Li
ABSTRACT

Precise glycosylation plays a crucial and distinctive role in thymic T cell development. The core fucosylation is dramatically up-regulated at the transition from CD4-CD8- (DN) to CD4+CD8+ (DP) in the thymic development. Ablation of core fucosylation in T cells did reduce the size of the thymus due to a significant loss of CD4+ SP, CD8+ SP and DP thymocytes in core fucosyltransferase (Fut8) knockout (Fut8-/-) mice. T cell receptors (TCRs) are heavily core fucosylated glycoproteins. Loss of core fucosylation of TCR contributed to the reduced phosphorylation of ZAP70 (pZAP70) in Fut8-/- DP cells was observed. Compare to the Fut8+/+OT-II DP thymocytes, pZAP70 was significantly reduced in Fut8-/- OT-II DP thymocytes with OVA323-339 stimulation. Also, the pZAP70 of Fut8+/+OT-I DP thymocytes with OVA257-264 stimulation was remarkably attenuated by treatment of the fucosidase. Upon anti-CD3/CD28 Abs stimulation, the increased apoptosis was found in Fut8-/- thymocytes compared with Fut8+/+ thymocytes. Moreover, the TCRhiCD69hi (post-positive selection thymocytes) was markedly depleted in the Fut8-/- thymus without any stimulation. The expression of CD5 was significantly down-regulated on the DP cells in the Fut8-/- thymus. Our results therefore demonstrate that ablation of core fucosylation results in the abnormal T cell development due to the attenuated signaling via TCR.

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Propidium iodide, ≥94.0% (HPLC)