title: Deletion of RBP-J in dendritic cells compromises TLR-mediated DC activation accompanied by abnormal cytoskeleton reorganization.
abstract: 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-γ 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.
authors.affiliation: Department of Hematology, Tangdu Hospital, Fourth Military Medical University, Xi'an, 710038, China.
authors.forename: Yun-Ru
authors.initials: YR
authors.lastname: Chen
authors.forename: Fan
authors.initials: F
authors.lastname: Feng
authors.forename: Li
authors.initials: L
authors.lastname: Wang
authors.forename: Shuo-Yao
authors.initials: SY
authors.lastname: Qu
authors.forename: Zhen-Qiang
authors.initials: ZQ
authors.lastname: Zhang
authors.forename: Li
authors.initials: L
authors.lastname: Liu
authors.forename: Hong-Yan
authors.initials: HY
authors.lastname: Qin
authors.forename: Ying-Min
authors.initials: YM
authors.lastname: Liang
authors.forename: Hua
authors.initials: H
authors.lastname: Han
mesh_terms: D048868:Adaptor Proteins, Signal Transducing; D000818:Animals; D002118:Calcium / Q000378:metabolism; D002135:Calcium-Binding Proteins / Q000235:genetics / Q000378:metabolism; D002450:Cell Communication; D002478:Cells, Cultured; D003598:Cytoskeletal Proteins / Q000378:metabolism*; D003713:Dendritic Cells / Q000276:immunology / Q000378:metabolism* / Q000648:ultrastructure; D017353:Gene Deletion; D051819:Immunoglobulin J Recombination Signal Sequence-Binding Protein / Q000172:deficiency / Q000235:genetics*; D036341:Intercellular Signaling Peptides and Proteins / Q000235:genetics / Q000378:metabolism; D016753:Interleukin-10 / Q000378:metabolism; D018664:Interleukin-12 / Q000378:metabolism; D047908:Intracellular Signaling Peptides and Proteins / Q000235:genetics / Q000378:metabolism; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D051880:Receptors, Notch / Q000378:metabolism; D000072099:Serrate-Jagged Proteins; D015398:Signal Transduction; D013601:T-Lymphocytes / Q000502:physiology; D051193:Toll-Like Receptors / Q000378:metabolism*; D015854:Up-Regulation
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D002135:Calcium-Binding Proteins; D003598:Cytoskeletal Proteins; C519665:DLL4 protein, mouse; C512925:Dlk1 protein, mouse; C556062:IL10 protein, mouse; D051819:Immunoglobulin J Recombination Signal Sequence-Binding Protein; D036341:Intercellular Signaling Peptides and Proteins; D047908:Intracellular Signaling Peptides and Proteins; D008565:Membrane Proteins; C497571:Rbpj protein, mouse; D051880:Receptors, Notch; D000072099:Serrate-Jagged Proteins; D051193:Toll-Like Receptors; D016753:Interleukin-10; D018664:Interleukin-12; D002118:Calcium