Cited by 1,301Immunotherapy and Immune ResponsesImmune Response and InflammationT-cell and B-cell Immunology

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Human dendritic cell subsets: an update

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Collin, Matthew, Bigley, Venetia·2018·Immunology

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Abstract

Dendritic cells (DC) are a class of bone-marrow-derived cells arising from lympho-myeloid haematopoiesis that form an essential interface between the innate sensing of pathogens and the activation of adaptive immunity. This task requires a wide range of mechanisms and responses, which are divided between three major DC subsets: plasmacytoid DC (pDC), myeloid/conventional DC1 (cDC1) and myeloid/conventional DC2 (cDC2). Each DC subset develops under the control of a specific repertoire of transcription factors involving differential levels of IRF8 and IRF4 in collaboration with PU.1, ID2, E2-2, ZEB2, KLF4, IKZF1 and BATF3. DC haematopoiesis is conserved between mammalian species and is distinct from monocyte development. Although monocytes can differentiate into DC, especially during inflammation, most quiescent tissues contain significant resident populations of DC lineage cells. An extended range of surface markers facilitates the identification of specific DC subsets although it remains difficult to dissociate cDC2 from monocyte-derived DC in some settings. Recent studies based on an increasing level of resolution of phenotype and gene expression have identified pre-DC in human blood and heterogeneity among cDC2. These advances facilitate the integration of mouse and human immunology, support efforts to unravel human DC function in vivo and continue to present new translational opportunities to medicine.

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Background
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Background
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Method
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Background
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Background
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Background
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Background
Characterizing the role of the immune microenvironment in multiple myeloma progression at a single-cell level
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Background
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“[9] This is accomplished primarily through a tightly regulated toll-like receptor (TLR)7/9-MyD88-IRF7 pathway-mediated sensing of nucleic acid sequences and by functioning as antigen presenting cells in concert with other subsets of myeloid dendritic cells.”
Background
Histiocytic and Dendritic Cell Sarcomas of Hematopoietic Origin Share Targetable Genomic Alterations Distinct from Follicular Dendritic Cell Sarcoma
Massoth, L. R., Hung, Y. P., Ferry, J. A., Hasserjian, R. P., Nardi, V., Nielsen, G. P., Sadigh, S., Venkataraman, V., Selig, M. K., Friedmann, A. M., et al. (2021) · The Oncologist · doi:10.1002/onco.13801 · Cited by 67
SCITO-seq: single-cell combinatorial indexed cytometry sequencing
Hwang, B., Lee, D. S., Tamaki, W., Sun, Y., Ogorodnikov, A., Hartoularos, G. C., Winters, A. F., Yeung, B. Z., Nazor, K. L., Song, Y. S., et al. (2021) · Nature Methods · doi:10.1038/s41592-021-01222-3 · Cited by 65
Bone marrow dendritic cells regulate hematopoietic stem/progenitor cell trafficking
Zhang, J., Supakorndej, T., Krambs, J. R., Rao, M., Abou‐Ezzi, G., Ye, R. Y., Li, S., Trinkaus, K. M., & Link, D. C. (2019) · Journal of Clinical Investigation · doi:10.1172/jci124829 · Cited by 60
“Moreover, the majority of DCs in human bone marrow express CD1c but not CD141, and do not express CD45RA, consistent with a mature cDC2 phenotype (Figure 1G, and Supplemental Figure 1B) (20, 22).”
Background
Dendritic Cell Vaccines in Ovarian Cancer
Zhang, X., He, T., Li, Y., Chen, L., Liu, H., Wu, Y., & Guo, H. (2021) · Frontiers in Immunology · doi:10.3389/fimmu.2020.613773 · Cited by 65
“cDC1 is the main DC subtype that activates CD8 T cells through the antigen cross-presentation process (29), while cDC2 secretes IL10, IL-12, IL-23, and TNF-b to stimulate the differentiation of the CD4T cells (30).”
Background
Role of Innate Immunity in Allergic Contact Dermatitis: An Update
Yamaguchi, H. L., Yamaguchi, Y., & Peeva, E. (2023) · International Journal of Molecular Sciences · doi:10.3390/ijms241612975 · Cited by 70
“Mo-DCs are derived from blood monocytes and migrate into the tissue in the inflammatory state including skin sensitization.”
BackgroundInfluential
Immune tolerance and the prevention of autoimmune diseases essentially depend on thymic tissue homeostasis
Shirafkan, F., Hensel, L., & Rattay, K. (2024) · Frontiers in Immunology · doi:10.3389/fimmu.2024.1339714 · Cited by 67
“Instead, cDC2s are de ﬁ ned by their surface expression of CD11b and CD172a (SIRP a ), are developmentally dependent on IRF4, IRF2 and RelB, and preferentially activate CD4 + helper T cell responses (171, 172).”
Background
Innate Immunity and Synovitis: Key Players in Osteoarthritis Progression
Panichi, V., Costantini, S., Grasso, M., Arciola, C. R., & Dolzani, P. (2024) · International Journal of Molecular Sciences · doi:10.3390/ijms252212082 · Cited by 66
“On the other hand, cDC2s produce higher quantities of IL-12 and are potent activators of Th1, Th2, Th17, and CD8+ T cells [107,108].”
Dendritic Cells, the Double Agent in the War Against HIV-1
Martín-Moreno, A., & Muñoz‐Fernández, M. Á. (2019) · Frontiers in Immunology · doi:10.3389/fimmu.2019.02485 · Cited by 69
IL-3 in the development and function of basophils
Varricchi, G., Poto, R., Marone, G., & Schroeder, J. T. (2021) · Seminars in Immunology · doi:10.1016/j.smim.2021.101510 · Cited by 63
Deubiquitinating enzyme OTUB1 in immunity and cancer: Good player or bad actor?
Liao, Y., Yang, M., Wang, K., Wang, Y., Zhong, B., & Jiang, N. (2021) · Cancer Letters · doi:10.1016/j.canlet.2021.12.002 · Cited by 63
Role of the innate and adaptive immune responses in the pathogenesis of systemic lupus erythematosus
Bolouri, N., Akhtari, M., Farhadi, E., Mansouri, R., Faezi, S. T., Jamshidi, A., & Mahmoudi, M. (2022) · Inflammation Research · doi:10.1007/s00011-022-01554-6 · Cited by 62
Glycolysis in Innate Immune Cells Contributes to Autoimmunity
Xu, Y., Chen, Y., Zhang, X., Ma, J., Liu, Y., Cui, L., & Wang, F. (2022) · Frontiers in Immunology · doi:10.3389/fimmu.2022.920029 · Cited by 64
The role of dendritic cells and their immunometabolism in rheumatoid arthritis
Suwa, Y., Nagafuchi, Y., Yamada, S., & Fujio, K. (2023) · Frontiers in Immunology · doi:10.3389/fimmu.2023.1161148 · Cited by 63
Exploring neutrophil extracellular traps: mechanisms of immune regulation and future therapeutic potential
Gao, F., Peng, H., Gou, R., Zhou, Y., Ren, S., & Li, F. (2025) · Experimental Hematology and Oncology · doi:10.1186/s40164-025-00670-3 · Cited by 68
“DCs, particularly plasmacytoid DCs (pDCs) and myeloid DCs (mDCs), serve as a crucial link between NET immunogenicity and adaptive immune responses [117].”
Metabolic regulation of dendritic cell activation and immune function during inflammation
Wu, L., Yan, Z., Jiang, Y., Chen, Y., Du, J., Guo, L., Xu, J., Luo, Z., & Liu, Y. (2023) · Frontiers in Immunology · doi:10.3389/fimmu.2023.1140749 · Cited by 62
MCT1 lactate transporter blockade re-invigorates anti-tumor immunity through metabolic rewiring of dendritic cells in melanoma
Niveau, C., Cettour-Cave, M., Mouret, S., Cuevas, E. S., Pezet, M., Roubinet, B., Gil, H., de Fraipont, F., Landemarre, L., Charles, J., et al. (2025) · Nature Communications · doi:10.1038/s41467-025-56392-x · Cited by 58
Monocyte-Derived Dendritic Cell Differentiation in Inflammatory Arthritis Is Regulated by the JAK/STAT Axis via NADPH Oxidase Regulation
Marzaioli, V., Canavan, M., Floudas, A., Wade, S. C., Low, C., Veale, D. J., & Fearon, U. (2020) · Frontiers in Immunology · doi:10.3389/fimmu.2020.01406 · Cited by 57
A T-cell-based immunogenicity protocol for evaluating human antigen-specific responses
Bozkus, C. C., Blazquez, A. B., Enokida, T., & Bhardwaj, N. (2021) · STAR Protocols · doi:10.1016/j.xpro.2021.100758 · Cited by 57
“Furthermore, PBMCs include multiple antigenpresenting cell (APC) populations, such as monocytes and dendritic cells (DCs), including conventional (cDCs) and plasmacytoid (pDCs) subsets (Collin and Bigley, 2018).”
Background
Imaging dendritic cell functions*
Bošnjak, B., Do, K. T. H., Förster, R., & Hammerschmidt, S. I. (2021) · Immunological Reviews · doi:10.1111/imr.13050 · Cited by 59
Hepatic Dendritic Cells, the Tolerogenic Liver Environment, and Liver Disease
Dou, L., Ono, Y., Chen, Y.-F., Chen, X., & Thomson, A. W. (2018) · Seminars in Liver Disease · doi:10.1055/s-0038-1646949 · Cited by 60
Select hyperactivating NLRP3 ligands enhance the T H 1- and T H 17-inducing potential of human type 2 conventional dendritic cells
Hatscher, L., Lehmann, C. H. K., Purbojo, A., Onderka, C., Liang, C., Hartmann, A., Cesnjevar, R. A., Bruns, H., Groß, O., Nimmerjahn, F., et al. (2021) · Science Signaling · doi:10.1126/scisignal.abe1757 · Cited by 60
Dendritic Cells and SARS-CoV-2 Infection: Still an Unclarified Connection
Campana, P., Parisi, V., Leosco, D., Bencivenga, D., Ragione, F. D., & Borriello, A. (2020) · Cells · doi:10.3390/cells9092046 · Cited by 55
Innate Immune Response to SARS-CoV-2 Infection: From Cells to Soluble Mediators
Ricci, D., Etna, M. P., Rizzo, F., Sandini, S., Severa, M., & Coccia, E. M. (2021) · International Journal of Molecular Sciences · doi:10.3390/ijms22137017 · Cited by 61
“Three DC subpopulations are present in the lung: conventional DC (cDC), including the CD141+ cDC1 population (mainly activating a Th1 response); the CD1c+ cDC2 population (responsible for regulation and production of pro-inflammatory chemokines); and CD123high pDC [86].”
Background
The Importance of Metabolism for Immune Homeostasis in Allergic Diseases
Rodríguez‐Coira, J., Villaseñor, A., Izquierdo, E., Huang, M., Barker‐Tejeda, T. C., Radzikowska, U., Sokołowska, M., & Barber, D. (2021) · Frontiers in Immunology · doi:10.3389/fimmu.2021.692004 · Cited by 58
Single-Cell RNA Sequencing Reveals Cellular and Transcriptional Changes Associated With M1 Macrophage Polarization in Hidradenitis Suppurativa
Mariottoni, P. R. C. G. B., Jiang, S. W., Prestwood, C. A., Jain, V., Suwanpradid, J., Whitley, M. J., Coates, M., Brown, D. A., Erdmann, D., Corcoran, D. L., et al. (2021) · Frontiers in Medicine · doi:10.3389/fmed.2021.665873 · Cited by 53
““Classical” or “conventional” DCs (cDC) can be classified in two types: cDC1 and cDC2 (81).”
BackgroundInfluential
Vitamin C enhances NF-κB-driven epigenomic reprogramming and boosts the immunogenic properties of dendritic cells
Morante-Palacios, O., Godoy‐Tena, G., Calafell-Segura, J., Ciudad, L., Martínez-Cáceres, E. M., Sardina, J. L., & Ballestar, E. (2022) · Nucleic Acids Research · doi:10.1093/nar/gkac941 · Cited by 57
“Furthermore, monocyte-derived DCs (moDCs) can be differentiated in vitro from monocytes (MOs), with GM-CSF and IL-4 (2). moDCs have been classically used as a convenient model that mimics blood DCs, especially cDC2 (3).”
Method
Single-cell resolution landscape of equine peripheral blood mononuclear cells reveals diverse cell types including T-bet+ B cells
Patel, R. S., Tomlinson, J. E., Divers, T. J., de Walle, G. R. V., & Rosenberg, B. R. (2021) · BMC Biology · doi:10.1186/s12915-020-00947-5 · Cited by 54
“markers for cDC1 in humans and mice [30] (in mice, CLEC9A is also expressed on plasmacytoid DC [31]).”
BackgroundResult
Transcriptome landscape of myeloid cells in human skin reveals diversity, rare populations and putative DC progenitors
Xue, D., Tabib, T., Morse, C., & Lafyatis, R. (2019) · Journal of Dermatological Science · doi:10.1016/j.jdermsci.2019.11.012 · Cited by 54
Friends with Benefits: Chemokines, Glioblastoma-Associated Microglia/Macrophages, and Tumor Microenvironment
Codrici, E., Popescu, I. D., Tănase, C., & Enciu, A. (2022) · International Journal of Molecular Sciences · doi:10.3390/ijms23052509 · Cited by 62
“DCs are classified into three groups, according to their immunophenotypic profile: classical DCs (cDC) and plasmacytoid DCs (pDC), which are present and active under steady-state conditions and monocyte-derived DCs (moDC), which arise only during inflammation [122].”
Background
Recent Progress in Dendritic Cell-Based Cancer Immunotherapy
Matsuo, K., Yoshie, O., Kitahata, K., Kamei, M., Hara, Y., & Nakayama, T. (2021) · Cancers · doi:10.3390/cancers13102495 · Cited by 54
“Recent studies have shown that pDCs are specialized for viral infection and rapidly produce large amounts of type I and III IFNs by activation via TLRs, while they have poor antigen-presenting capacity to naive T cells [41,61].”
BackgroundInfluential
Entinostat in combination with nivolumab in metastatic pancreatic ductal adenocarcinoma: a phase 2 clinical trial
Baretti, M., Danilova, L., Durham, J. N., Betts, C. B., Cope, L., Sidiropoulos, D. N., Tandurella, J. A., Charmsaz, S., Groß, N., Hernandez, A., et al. (2024) · Nature Communications · doi:10.1038/s41467-024-52528-7 · Cited by 59
“…components, including pre-Dendritic Cell (preDC)/classic monocytes (Lin-CD14 + CD16 - ), which are early progenitors to mature dendritic cells, non-classical monocytes (Lin - CD14 low CD16 + ), early myelocytes, plasmacytoid dendritic cells (pDC) and classical dendritic cells (cDCs) 18,19 .”
Influential
Dendritic Cell Subsets and Effector Function in Idiopathic and Connective Tissue Disease-Associated Pulmonary Arterial Hypertension
van Uden, D., Boomars, K. A., & Kool, M. (2019) · Frontiers in Immunology · doi:10.3389/fimmu.2019.00011 · Cited by 53
“Under steady state conditions, several DC subsets with unique functions can be identified (40, 41).”
Background
An immunologist’s guide to immunosenescence and its treatment
Caruso, C., Ligotti, M. E., Accardi, G., Aiello, A., & Candore, G. (2022) · Expert Review of Clinical Immunology · doi:10.1080/1744666x.2022.2106217 · Cited by 53
Immune cellular components and signaling pathways in the tumor microenvironment
Yenyuwadee, S., Aliazis, K., Wang, Q., Christofides, A., Shah, R., Patsoukis, N., & Boussiotis, V. A. (2022) · Seminars in Cancer Biology · doi:10.1016/j.semcancer.2022.08.004 · Cited by 54
Infection, modulation and responses of antigen-presenting cells to African swine fever viruses
Franzoni, G., Giudici, S. D., & Oggiano, A. (2018) · Virus Research · doi:10.1016/j.virusres.2018.10.007 · Cited by 54
Molecular Aspects of Dendritic Cell Activation in Leishmaniasis: An Immunobiological View
Tibúrcio, R., Nunes, S., Nunes, I. V., Ampuero, M. R., Bonyek-Silva, Í., Lima, R., Tavares, N. M., & Brodskyn, C. (2019) · Frontiers in Immunology · doi:10.3389/fimmu.2019.00227 · Cited by 53
“Interestingly, despite the significant importance of DCs in several immunological processes, these cells do not comprise a homogeneous population, and are further classified into distinct subtypes according to origin, differential expression of surface proteins, cell localization, and immunological function (15).”
BackgroundInfluential
Cross-Presenting XCR1+ Dendritic Cells as Targets for Cancer Immunotherapy
Audsley, K. M., McDonnell, A. M., & Waithman, J. C. (2020) · Cells · doi:10.3390/cells9030565 · Cited by 54
Tumor‐associated human dendritic cell subsets: Phenotype, functional orientation, and clinical relevance
Plesca, I., Müller, L., Böttcher, J. P., Medyouf, H., Wehner, R., & Schmitz, M. (2022) · European Journal of Immunology · doi:10.1002/eji.202149487 · Cited by 58
The Role of Immune Cells in the Pathogenesis of Idiopathic Pulmonary Fibrosis
Xu, Y., Lan, P., & Wang, T. (2023) · Medicina · doi:10.3390/medicina59111984 · Cited by 58
“Two main types of mature DCs have been identiﬁed: plasmacytoid DCs (pDCs) and myeloid DCs (mDCs) [65].”
Background
Decidual immune cells: Guardians of human pregnancies
Solano, M. E. (2019) · Best Practice & Research Clinical Obstetrics & Gynaecology · doi:10.1016/j.bpobgyn.2019.05.009 · Cited by 55
Plasmacytoid dendritic cells in the eye
Jamali, A., Kenyon, B. M., Ortiz, G., Abou-Slaybi, A., Sendra, V. G., Harris, D. L., & Hamrah, P. (2020) · Progress in Retinal and Eye Research · doi:10.1016/j.preteyeres.2020.100877 · Cited by 52
Depletion and Dysfunction of Dendritic Cells: Understanding SARS-CoV-2 Infection
Chang, T., Yang, J., Deng, H., Chen, D., Yang, X., & Tang, Z. (2022) · Frontiers in Immunology · doi:10.3389/fimmu.2022.843342 · Cited by 57
Polysialic Acid in the Immune System
Villanueva-Cabello, T. M., Gutiérrez-Valenzuela, L. D., Salinas-Marín, R., López-Guerrero, D. V., & Martínez-Duncker, I. (2022) · Frontiers in Immunology · doi:10.3389/fimmu.2021.823637 · Cited by 50
Understanding the bidirectional interactions between two-dimensional materials, microorganisms, and the immune system
Peng, G., & Fadeel, B. (2022) · Advanced Drug Delivery Reviews · doi:10.1016/j.addr.2022.114422 · Cited by 54
Digitaldlsorter: Deep-Learning on scRNA-Seq to Deconvolute Gene Expression Data
Torroja, C., & Sánchez‐Cabo, F. (2019) · Frontiers in Genetics · doi:10.3389/fgene.2019.00978 · Cited by 52
“Clusters C2 and C11 were considered monocyte derived based on CD14, PTPRC and ITGAX expression (Collin and Bigley, 2018) ( Figure 3 , Supplementary Figures 6 and 9 ).”
Enhanced NF-κB signaling in type-2 dendritic cells at baseline predicts non-response to adalimumab in psoriasis
Ejarque, R. A., Ale, H. B., Grys, K., Tosi, I., Solanky, S., Ainali, C., Catak, Z., Sreeneebus, H., Saklatvala, J. R., Dand, N., et al. (2021) · Nature Communications · doi:10.1038/s41467-021-25066-9 · Cited by 51

Authors: Collin, M., & Bigley, V.
Affiliations: Newcastle upon Tyne Hospitals NHS Foundation Trust (GB)
Corresponding author: Collin, Matthew
ORCID: Collin, Matthew
Bigley, Venetia
Venue: Immunology
Publisher: Wiley
Published: 2018-02-27
Volume: 154
Issue: 1
Pages: 3-20
ISSN: 0019-2805 (ISSN-L)
1365-2567
DOI: 10.1111/imm.12888
PMC: PMC5904714
OpenAlex: W2781617771
Cited by: 1,301
References: 203
Citations by year: 2026: 69 · 2025: 169 · 2024: 167 · 2023: 191 · 2022: 237 · 2021: 198 · 2020: 155 · 2019: 87 · 2018: 27
FWCI: 11.83
Type: journal article
Language: en
Open access: hybrid
doi.org
Licence: cc-by
creativecommons.org/licenses/by/4.0/ (vor)
Locations: Immunology (publishedVersion, cc-by)
Europe PMC (PubMed Central) (publishedVersion, cc-by)
PubMed Central (publishedVersion, cc-by)
PubMed (publishedVersion)
Newcastle University ePrints (Newcastle Univesity) (cc-by)
Funders: Cancer Research UK (C30484/A21025)
Wellcome Trust (101155/Z/13/Z)
Topics: Life Sciences › Immunology and Microbiology › Immunology › Immunotherapy and Immune Responses
Life Sciences › Immunology and Microbiology › Immunology › Immune Response and Inflammation
Life Sciences › Immunology and Microbiology › Immunology › T-cell and B-cell Immunology
Keywords: dendritic cells, dendritic cell subsets, plasmacytoid dendritic cells, myeloid dendritic cells, DC1, DC2, transcription factors, IRF8, IRF4, PU.1, monocyte-derived dendritic cells, cell surface markers, innate immunity, adaptive immunity
MeSH terms: Kruppel-Like Factor 4, Cell Communication, Cell Differentiation, Dendritic Cells, Humans, Immunity, Phenotype, Signal Transduction, Biomarkers, Immunophenotyping

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Human dendritic cell subsets: an update

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