التفاصيل البيبلوغرافية
| العنوان: |
Control of TNF-Induced Dendritie Cell Maturation by Hybrid-Type N-Glycans. |
| المؤلفون: |
Schlickeiser, Stephan1, Stanojlovic, Svetlana2, Appelt, Christine1, Vogt, Katrin1, Vogel, Simone1, Haase, Stefanie1, Ritter, Thomas3, Volk, Hans-Dieter1,4, Pleyer, Uwe5, Sawitzki, Birgit1 birgit.sawitzki@charite.de |
| المصدر: |
Journal of Immunology. 5/1/2011, Vol. 186 Issue 9, p5201-5211. 11p. |
| مصطلحات موضوعية: |
*DENDRITIC cells, *TUMOR necrosis factors, *BONE marrow, *MANNOSIDASES, *MESSENGER RNA, *T cells, *CELL migration |
| مستخلص: |
The activity of α-1,2-mannosidase I is required for the conversion of high-mannose to hybrid-type (ConA reactive) and complex-type N-glycans (Phaseolus vulgaris-leukoagglutinin [PHA-L] reactive) during posttranslational protein N-glycosylation. We recently demonstrated that α-1,2-mannosidase I mRNA decreases in graft-infiltrating CD11c+ dendritic cells (DCs) prior to allograft rejection. Although highly expressed in immature DCs, little is known about its role in DC functions. In this study, analysis of surface complex-type N-glycan expression by lectin staining revealed the existence of PHA-Llow and PHA-Lhigh subpopulations in murine splenic conventional DCs, as well as in bone marrow-derived DC (BMDCs), whereas plasmacytoid DCs are nearly exclusively PHA-Lhigh. Interestingly, all PHA-Lhigh DCs displayed a strongly reduced responsiveness to TNF-α-induced p38-MAPK activation compared with PHA-Llow DCs, indicating differences in PHA-L-binding capacities between DCs with different inflammatory properties. However, p38 phosphorylation levels were increased in BMDCs overexpressing α-1,2-mannosidase I mRNA. Moreover, hybrid-type, but not complex-type, N-glycans are required for TNF-α-induced p38-MAPK activation and subsequent phenotypic maturation of BMDCs (MHC-II, CD86, CCR7 upregulation). α-1,2-mannosidase I inhibitor-treated DCs displayed diminished transendothelial migration in response to CCL19, homing to regional lymph nodes, and priming of IFN-γ-producing T cells in vivo. In contrast, the activity of α-1,2-mannosidase I is dispensable for LPS-induced signaling, as well as the DCs' general capability for phenotypic and functional maturation. Systemic application of an α-1,2-mannosidase I inhibitor was able to significantly prolong allograft survival in a murine high-responder corneal transplantation model, further highlighting the importance of N-glycan processing by α-1,2-mannosidase I for alloantigen presentation and T cell priming. [ABSTRACT FROM AUTHOR] |
| قاعدة البيانات: |
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