Phenotypical Diversification of Early IFNα-Producing Human Plasmacytoid Dendritic Cells Using Droplet-Based Microfluidics
Plasmacytoid dendritic cells (pDCs) are a rare type of highly versatile immune cells that besides their specialized function of massive type I interferon (IFN-I) production are able to exert cytotoxic effector functions. However, diversification upon toll like receptor (TLR)-induced activation leads...
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2021-04-01
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| Series: | Frontiers in Immunology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fimmu.2021.672729/full |
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| author | Laura C. Van Eyndhoven Laura C. Van Eyndhoven Eleni Chouri Eleni Chouri Nikita Subedi Nikita Subedi Jurjen Tel Jurjen Tel |
| author_facet | Laura C. Van Eyndhoven Laura C. Van Eyndhoven Eleni Chouri Eleni Chouri Nikita Subedi Nikita Subedi Jurjen Tel Jurjen Tel |
| author_sort | Laura C. Van Eyndhoven |
| collection | DOAJ |
| description | Plasmacytoid dendritic cells (pDCs) are a rare type of highly versatile immune cells that besides their specialized function of massive type I interferon (IFN-I) production are able to exert cytotoxic effector functions. However, diversification upon toll like receptor (TLR)-induced activation leads to highly heterogeneous responses that have not been fully characterized yet. Using droplet-based microfluidics, we showed that upon TLR7/8 and TLR9-induced single-cell activation only 1-3% secretes IFNα, and only small fractions upregulate cytotoxicity markers. Interestingly, this 1-3% of early IFN-producing pDCs, also known as first responders, express high levels of programmed death-ligand 1 (PD-L1) and TNF-related apoptosis-inducing ligand (TRAIL), which makes these hybrid cells similar to earlier described IFN-I producing killer pDCs (IKpDCs). IFN-I priming increases the numbers of IFNα producing cells up to 40%, but does not significantly upregulate the cytotoxicity markers. Besides, these so-called second responders do not show a cytotoxic phenotype as potent as observed for the first responders. Overall, our results indicate that the first responders are the key drivers orchestrating population wide IFN-I responses and possess high cytotoxic potential. |
| first_indexed | 2024-12-17T21:09:36Z |
| format | Article |
| id | doaj.art-43aa5e1a53c84100abbf0d9173b11db4 |
| institution | Directory Open Access Journal |
| issn | 1664-3224 |
| language | English |
| last_indexed | 2024-12-17T21:09:36Z |
| publishDate | 2021-04-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Immunology |
| spelling | doaj.art-43aa5e1a53c84100abbf0d9173b11db42022-12-21T21:32:29ZengFrontiers Media S.A.Frontiers in Immunology1664-32242021-04-011210.3389/fimmu.2021.672729672729Phenotypical Diversification of Early IFNα-Producing Human Plasmacytoid Dendritic Cells Using Droplet-Based MicrofluidicsLaura C. Van Eyndhoven0Laura C. Van Eyndhoven1Eleni Chouri2Eleni Chouri3Nikita Subedi4Nikita Subedi5Jurjen Tel6Jurjen Tel7Laboratory of Immunoengineering, Department of Biomedical Engineering, Eindhoven University of Technology, Eindhoven, NetherlandsInstitute for Complex Molecular Systems (ICMS), Eindhoven University of Technology, Eindhoven, NetherlandsLaboratory of Immunoengineering, Department of Biomedical Engineering, Eindhoven University of Technology, Eindhoven, NetherlandsInstitute for Complex Molecular Systems (ICMS), Eindhoven University of Technology, Eindhoven, NetherlandsLaboratory of Immunoengineering, Department of Biomedical Engineering, Eindhoven University of Technology, Eindhoven, NetherlandsInstitute for Complex Molecular Systems (ICMS), Eindhoven University of Technology, Eindhoven, NetherlandsLaboratory of Immunoengineering, Department of Biomedical Engineering, Eindhoven University of Technology, Eindhoven, NetherlandsInstitute for Complex Molecular Systems (ICMS), Eindhoven University of Technology, Eindhoven, NetherlandsPlasmacytoid dendritic cells (pDCs) are a rare type of highly versatile immune cells that besides their specialized function of massive type I interferon (IFN-I) production are able to exert cytotoxic effector functions. However, diversification upon toll like receptor (TLR)-induced activation leads to highly heterogeneous responses that have not been fully characterized yet. Using droplet-based microfluidics, we showed that upon TLR7/8 and TLR9-induced single-cell activation only 1-3% secretes IFNα, and only small fractions upregulate cytotoxicity markers. Interestingly, this 1-3% of early IFN-producing pDCs, also known as first responders, express high levels of programmed death-ligand 1 (PD-L1) and TNF-related apoptosis-inducing ligand (TRAIL), which makes these hybrid cells similar to earlier described IFN-I producing killer pDCs (IKpDCs). IFN-I priming increases the numbers of IFNα producing cells up to 40%, but does not significantly upregulate the cytotoxicity markers. Besides, these so-called second responders do not show a cytotoxic phenotype as potent as observed for the first responders. Overall, our results indicate that the first responders are the key drivers orchestrating population wide IFN-I responses and possess high cytotoxic potential.https://www.frontiersin.org/articles/10.3389/fimmu.2021.672729/fullplasmacytoid dendritic cellsdroplet-based microfluidicsdiversificationheterogeneityinterferonscytotoxicity |
| spellingShingle | Laura C. Van Eyndhoven Laura C. Van Eyndhoven Eleni Chouri Eleni Chouri Nikita Subedi Nikita Subedi Jurjen Tel Jurjen Tel Phenotypical Diversification of Early IFNα-Producing Human Plasmacytoid Dendritic Cells Using Droplet-Based Microfluidics Frontiers in Immunology plasmacytoid dendritic cells droplet-based microfluidics diversification heterogeneity interferons cytotoxicity |
| title | Phenotypical Diversification of Early IFNα-Producing Human Plasmacytoid Dendritic Cells Using Droplet-Based Microfluidics |
| title_full | Phenotypical Diversification of Early IFNα-Producing Human Plasmacytoid Dendritic Cells Using Droplet-Based Microfluidics |
| title_fullStr | Phenotypical Diversification of Early IFNα-Producing Human Plasmacytoid Dendritic Cells Using Droplet-Based Microfluidics |
| title_full_unstemmed | Phenotypical Diversification of Early IFNα-Producing Human Plasmacytoid Dendritic Cells Using Droplet-Based Microfluidics |
| title_short | Phenotypical Diversification of Early IFNα-Producing Human Plasmacytoid Dendritic Cells Using Droplet-Based Microfluidics |
| title_sort | phenotypical diversification of early ifnα producing human plasmacytoid dendritic cells using droplet based microfluidics |
| topic | plasmacytoid dendritic cells droplet-based microfluidics diversification heterogeneity interferons cytotoxicity |
| url | https://www.frontiersin.org/articles/10.3389/fimmu.2021.672729/full |
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