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

First Author  Liang W Year  2019
Journal  Mol Immunol Volume  112
Pages  312-321 PubMed ID  31229844
Mgi Jnum  J:340409 Mgi Id  MGI:7529315
Doi  10.1016/j.molimm.2019.06.011 Citation  Liang W, et al. (2019) Ablation of core fucosylation attenuates the signal transduction via T cell receptor to suppress the T cell development. Mol Immunol 112:312-321
abstractText  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 OVA(323-339) stimulation. Also, the pZAP70 of Fut8(+/+)OT-I DP thymocytes with OVA(257-264) 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 TCR(hi)CD69(hi) (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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