title: Induction of CD4+ CD25+ Foxp3+ T regulatory cells by dendritic cells derived from ILT3 lentivirus-transduced human CD34+ cells.
abstract: Immunoglobulin-like transcript 3 (ILT3) belongs to a family of inhibitory receptors with cytoplasmic immunoreceptor tyrosine based inhibitory motifs (ITIMs). Numerous studies have reported that increased ILT3 expression is associated with the tolerogenic properties of antigen-presenting cells (APCs) including dendritic cells (DCs). In this study, human CD34(+) hematopoietic stem/progenitor cells (HPSCs) were transduced with self-inactivating lentiviral vector carrying the ILT3 gene, and then induced to differentiate into DCs. Long-term and sustained transgene expression were observed. Importantly, DCs differentiated from ILT3-transduced HPSCs expressed high levels of human ILT3 and acquired strong tolerogenic capacity. This effect was associated with markedly decreased expression of co-stimulatory molecules (CD80, CD86) and down-regulation of NF-κB. Functionally, ILT3(high) DCs showed a reduced capacity to stimulate allogeneic T cell proliferation and increased the production of CD4(+)CD25(+)Foxp3(+) T regulatory cells with immunosuppressive activity. These results demonstrate that DCs derived from ILT3-transduced human CD34(+)HPSCs display tolerogenic properties to induce T regulatory cells in vitro.
authors: Department of Renal Transplant, Center of Nephropathy, The First Affiliated Hospital, Medical College, Xi'an Jiaotong University, Xi'an, 710061 Shaanxi, China.
authors: Guanqun
authors: G
authors: Ge
authors: Puxun
authors: P
authors: Tian
authors: Hongbao
authors: H
authors: Liu
authors: Jin
authors: J
authors: Zheng
authors: Xiaohu
authors: X
authors: Fan
authors: Chenguang
authors: C
authors: Ding
authors: Zhankui
authors: Z
authors: Jin
authors: Xiaohui
authors: X
authors: Luo
authors: Wujun
authors: W
authors: Xue
mesh_terms: D018122:B7-1 Antigen / Q000378:metabolism; D051940:B7-2 Antigen / Q000378:metabolism; D002454:Cell Differentiation / Q000276:immunology; D002478:Cells, Cultured; D003713:Dendritic Cells / Q000276:immunology* / Q000378:metabolism; D015536:Down-Regulation / Q000276:immunology; D051858:Forkhead Transcription Factors / Q000276:immunology* / Q000378:metabolism; D005822:Genetic Vectors / Q000235:genetics; D006412:Hematopoietic Stem Cells / Q000378:metabolism; D006801:Humans; D007108:Immune Tolerance; D007166:Immunosuppressive Agents / Q000378:metabolism; D016086:Lentivirus; D008213:Lymphocyte Activation / Q000276:immunology; D008562:Membrane Glycoproteins; D016328:NF-kappa B / Q000378:metabolism; D011956:Receptors, Cell Surface / Q000235:genetics / Q000276:immunology*; D011971:Receptors, Immunologic; D050378:T-Lymphocytes, Regulatory / Q000166:cytology / Q000276:immunology* / Q000378:metabolism; D014161:Transduction, Genetic; D019076:Transgenes
chemical_list: D018122:B7-1 Antigen; D051940:B7-2 Antigen; C418974:FOXP3 protein, human; D051858:Forkhead Transcription Factors; D007166:Immunosuppressive Agents; C107907:LILRB4 protein, human; D008562:Membrane Glycoproteins; D016328:NF-kappa B; D011956:Receptors, Cell Surface; D011971:Receptors, Immunologic