DLL4⁺ dendritic cells: Key regulators of Notch Signaling in effector T cell responses

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• 作者：Lijun Meng^a ; Shaoyan Hu^b ; Jian Wang^b ; Shan He^a ; Yi Zhang ; MD ; PhD^a ; ^c ; ^{yi.zhang@temple.edu" class="auth_mail" title="E-mail the corresponding author}
• 关键词：APC ; antigen presenting cell ; CTL ; cytotoxic T lymphocyte ; DC ; dendritic cell ; cDC ; conventional dendritic cell ; pDC ; plasmacytoid dendritic cell ; CMP ; common myeloid progenitor ; HPC ; hematopoietic progenitor cell ; MDP ; macrophage and DC progenitor ; HSCT ; hematopoietic stem cell transplantation ; DLL ; delta-like ligand ; GVHD ; graft-versus-host disease ; NICD ; Notch intracellular domain ; moDC ; monocyte-derived dendritic cell ; Th ; T helper ; TLR ; toll-like receptor ; TCR ; T cell receptor
• 刊名：Pharmacological Research
• 出版年：2016
• 出版时间：November 2016
• 年：2016
• 卷：113
• 期：part_PA
• 页码：449-457
• 全文大小：990 K

文摘

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.