PMID- 23138187 OWN - NLM STAT- MEDLINE DCOM- 20130617 LR - 20211021 IS - 1573-4978 (Electronic) IS - 0301-4851 (Linking) VI - 40 IP - 2 DP - 2013 Feb TI - Deletion of RBP-J in dendritic cells compromises TLR-mediated DC activation accompanied by abnormal cytoskeleton reorganization. PG - 1531-9 LID - 10.1007/s11033-012-2198-3 [doi] AB - Dendritic cells (DCs) are professional antigen presenting cells that activate and modulate immune responses, but the mechanisms underlying DC activation have not been fully understood. In this study, we investigated the role of Notch signaling in DC activation by using murine bone marrow-derived DCs. Triggering of Toll-like receptors (TLRs) of DCs led to upregulated expression of Notch ligands. Disruption of Notch signaling by the deletion of RBP-J, the critical transcription factor mediating the canonical signaling from all Notch receptors, resulted in a reduced capacity of DCs in activating T cells. Moreover, RBP-J deficiency altered the polarization of T cell activation, as manifested by downregulated interferon-gamma and upregulated interleukin-4 and -10 expressions after LPS or Poly(I:C) stimulation. Furthermore, we found that RBP-J(-/-) DCs had reduced intracellular calcium after TLR-triggering. Immunofluorescent staining showed that RBP-J deficient DCs exhibited attenuated cytoskeleton reorganization when contacting T cells. In summary, our results suggested that the canonical Notch signaling promotes the cytoskeleton reorganization and the TLR-mediated DC activation. FAU - Chen, Yun-Ru AU - Chen YR AD - Department of Hematology, Tangdu Hospital, Fourth Military Medical University, Xi'an, 710038, China. FAU - Feng, Fan AU - Feng F FAU - Wang, Li AU - Wang L FAU - Qu, Shuo-Yao AU - Qu SY FAU - Zhang, Zhen-Qiang AU - Zhang ZQ FAU - Liu, Li AU - Liu L FAU - Qin, Hong-Yan AU - Qin HY FAU - Liang, Ying-Min AU - Liang YM FAU - Han, Hua AU - Han H LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20121109 PL - Netherlands TA - Mol Biol Rep JT - Molecular biology reports JID - 0403234 RN - 0 (Adaptor Proteins, Signal Transducing) RN - 0 (Calcium-Binding Proteins) RN - 0 (Cytoskeletal Proteins) RN - 0 (DLL4 protein, mouse) RN - 0 (Dlk1 protein, mouse) RN - 0 (IL10 protein, mouse) RN - 0 (Immunoglobulin J Recombination Signal Sequence-Binding Protein) RN - 0 (Intercellular Signaling Peptides and Proteins) RN - 0 (Intracellular Signaling Peptides and Proteins) RN - 0 (Membrane Proteins) RN - 0 (Rbpj protein, mouse) RN - 0 (Receptors, Notch) RN - 0 (Serrate-Jagged Proteins) RN - 0 (Toll-Like Receptors) RN - 130068-27-8 (Interleukin-10) RN - 187348-17-0 (Interleukin-12) RN - SY7Q814VUP (Calcium) SB - IM MH - Adaptor Proteins, Signal Transducing MH - Animals MH - Calcium/metabolism MH - Calcium-Binding Proteins/genetics/metabolism MH - Cell Communication MH - Cells, Cultured MH - Cytoskeletal Proteins/*metabolism MH - Dendritic Cells/immunology/*metabolism/ultrastructure MH - Gene Deletion MH - Immunoglobulin J Recombination Signal Sequence-Binding Protein/deficiency/*genetics MH - Intercellular Signaling Peptides and Proteins/genetics/metabolism MH - Interleukin-10/metabolism MH - Interleukin-12/metabolism MH - Intracellular Signaling Peptides and Proteins/genetics/metabolism MH - Membrane Proteins/genetics/metabolism MH - Mice MH - Mice, Inbred C57BL MH - Mice, Transgenic MH - Receptors, Notch/metabolism MH - Serrate-Jagged Proteins MH - Signal Transduction MH - T-Lymphocytes/physiology MH - Toll-Like Receptors/*metabolism MH - Up-Regulation EDAT- 2012/11/10 06:00 MHDA- 2013/06/19 06:00 CRDT- 2012/11/10 06:00 PHST- 2012/05/07 00:00 [received] PHST- 2012/10/09 00:00 [accepted] PHST- 2012/11/10 06:00 [entrez] PHST- 2012/11/10 06:00 [pubmed] PHST- 2013/06/19 06:00 [medline] AID - 10.1007/s11033-012-2198-3 [doi] PST - ppublish SO - Mol Biol Rep. 2013 Feb;40(2):1531-9. doi: 10.1007/s11033-012-2198-3. Epub 2012 Nov 9.