title: DLL4+dendritic cells: Key regulators of Notch Signaling in effector T cell responses.
abstract: Dendritic cells (DCs) are critical regulators of adaptive immune responses. DCs can elicit primary T cell responses at low DC:T cell ratios through their expression of high levels of antigen-presenting molecules and costimulatory molecules. DCs are important for induction of functionally diverse T cell subsets such as CD4+T helper (Th)1 and Th17 cells and effector CD8+T cells able to reside in epithelial tissues. Recent studies begin illuminating the underlying mechanism by which DCs regulate specialized T cell subsets. DCs are composed of subsets that differ in their phenotype, localization and function. DCs expressing high levels of DLL4 (DLL4+DCs), which is a member of Notch ligand family, are newly discovered cells that have greater ability than DLL4-DCs to promote the generation of Th1 and Th17 CD4+T cells. DLL4 derived from DLL4+DCs is also important for promoting the differentiation and expansion of effector CD8+T cells. Experimental studies have demonstrated that selective deletion of DLL4 in DCs causes impaired antitumor immunity. In contrast, blocking DLL4 leads to dramatic reduction of inflammatory T cell responses and their-mediated tissue damage. We will discuss emerging functional specialization within the DLL4+DC compartment, DLL4+DC biology and the impact of pharmacological modulation of DLL4 to control inflammatory disorders.
authors.affiliation: Fels Institute for Cancer Research and Molecular Biology, Temple University, USA.
authors.forename: Lijun
authors.initials: L
authors.lastname: Meng
authors.affiliation: Department of Hematology, Children's Hospital, Soochow University, Suzhou, China.
authors.forename: Shaoyan
authors.initials: S
authors.lastname: Hu
authors.affiliation: Department of Hematology, Children's Hospital, Soochow University, Suzhou, China.
authors.forename: Jian
authors.initials: J
authors.lastname: Wang
authors.affiliation: Fels Institute for Cancer Research and Molecular Biology, Temple University, USA.
authors.forename: Shan
authors.initials: S
authors.lastname: He
authors.affiliation: Fels Institute for Cancer Research and Molecular Biology, Temple University, USA; Department of Microbiology and Immunology, Temple University, USA. Electronic address: yi.zhang@temple.edu.
authors.forename: Yi
authors.initials: Y
authors.lastname: Zhang
mesh_terms: D000818:Animals; D002454:Cell Differentiation / Q000276:immunology; D003713:Dendritic Cells / Q000276:immunology*; D006801:Humans; D007249:Inflammation / Q000276:immunology; D047908:Intracellular Signaling Peptides and Proteins / Q000276:immunology / Q000378:metabolism*; D008565:Membrane Proteins / Q000276:immunology / Q000378:metabolism*; D051880:Receptors, Notch / Q000276:immunology / Q000378:metabolism*; D015398:Signal Transduction / Q000276:immunology; D016176:T-Lymphocyte Subsets / Q000276:immunology*
chemical_list: D047908:Intracellular Signaling Peptides and Proteins; D008565:Membrane Proteins; D051880:Receptors, Notch; C064045:delta protein
keywords: Alloimmunity and autoimmunity; DLL4; DLL4(+) DCs; Notch signaling; Tumor immunity