Abstract
Dendritic cells (DCs) are potent and versatile professional antigen-presenting cells and central for the induction of adaptive immunity. The ability to migrate and transport peripherally acquired antigens to draining lymph nodes for subsequent cognate T cell priming is a key feature of DCs. Consequently, DC-based immunotherapies are used to elicit tumor-antigen specific T cell responses in cancer patients. Understanding chemokine-guided DC migration is critical to explore DCs as cellular vaccines for immunotherapeutic approaches. Currently, research is hampered by the lack of appropriate human cellular model systems to effectively study spatio-temporal signaling and CCR7-driven migration of human DCs. Here, we report that the previously established human neoplastic cell line CAL-1 expresses the human DC surface antigens CD11c and HLA-DR together with co-stimulatory molecules. Importantly, if exposed for three days to GM-CSF, CAL-1 cells induce the endogenous expression of the chemokine receptor CCR7 upon encountering the clinically approved TLR7/8 agonist Resiquimod R848 and readily migrate along chemokine gradients. Further, we demonstrate that CAL-1 cells can be genetically modified to express fluorescent (GFP)-tagged reporter proteins to study and visualize signaling or can be gene-edited using CRISPR/Cas9. Hence, we herein present the human CAL-1 cell line as versatile and valuable cellular model system to effectively study human DC migration and signaling.
Highlights
Dendritic cells (DCs) are sentinels of the innate and adaptive immune system and play essential roles in initiating, coordinating and regulating adaptive immune responses [1]
The human dendritic cell line CAL-1 originates from a patient with blastic natural killer cell lymphoma [30], a disease known as blastic plasmacytoid dendritic cell neoplasma [31]
The chemokine receptor CCR7, required for lymph node homing of DCs, was not detected on the surface of CAL-1 cells (Figure 1A)
Summary
Dendritic cells (DCs) are sentinels of the innate and adaptive immune system and play essential roles in initiating, coordinating and regulating adaptive immune responses [1]. They reside in peripheral tissues where they are poised to capture and process antigens derived from invading pathogens. CCR7-expressing DCs migrate along CCL19 and CCL21 chemokine gradients and via the lymph system to reach the T cell zone of the draining lymph node [15, 16]. Besides controlling DC homing, CCR7 coordinates the recruitment of circulating T cells from the blood to the lymph nodes and acts as co-stimulatory molecule to efficiently prime T cells [17]. CCL21 is not produced, but trapped and presented by human high endothelial venules (HEVs), whereas in mice this chemokine is synthesized directly by HEVs [19]
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