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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Liu, H., Lu, Y., Zong, J., Zhang, B., Li, X., Qi, H., Yu, T., & Li, Y. (2024) · Journal of Nanobiotechnology · doi:10.1186/s12951-024-02913-7 · Cited by 34
“Furthermore, cells resembling "MoDCs" generated during inflammation are now commonly classified as highly plastic or "non-classical" monocytes rather than true DCs [59].”
Background
Effective Activation of Human Antigen-Presenting Cells and Cytotoxic CD8+ T Cells by a Calcium Phosphate-Based Nanoparticle Vaccine Delivery System
Scheffel, F., Knuschke, T., Otto, L., Kollenda, S., Sokolova, V., Cosmovici, C., Buer, J., Timm, J., Epple, M., & Westendorf, A. M. (2020) · Vaccines · doi:10.3390/vaccines8010110 · Cited by 28
“pDCs express the intracellular TLRs 7 and 9, while cDCs respond through TLRs 1-6, 8, and 10 to lipopolysaccharide, flagellin, poly(I:C), and R848 [10,11].”
Background
Dual Pro- and Anti-Inflammatory Features of Monocyte-Derived Dendritic Cells
Azeem, W., Bakke, R. M., Appel, S., Oyan, A. M., & Kalland, K. (2020) · Frontiers in Immunology · doi:10.3389/fimmu.2020.00438 · Cited by 28
The Dynamic Interplay Between Mast Cells, Aging/Cellular Senescence, and Liver Disease
Kundu, D., Kennedy, L. L., Meadows, V., Baiocchi, L., Alpini, G. D., & Francis, H. (2020) · Gene Expression · doi:10.3727/105221620x15960509906371 · Cited by 28
A Two-Step Process of Effector Programming Governs CD4+ T Cell Fate Determination Induced by Antigenic Activation in the Steady State
Opejin, A., Surnov, A., Misulovin, Z., Pherson, M., Gross, C. J., Iberg, C. A., Fallahee, I., Bourque, J., Dorsett, D., & Hawiger, D. (2020) · Cell Reports · doi:10.1016/j.celrep.2020.108424 · Cited by 29
“cDCs are the major population among both human and murine DCs and can be further divided into the cDC1 and cDC2 subsets based on their development and expression of specific markers (Collin and Bigley, 2018; Durai and Murphy, 2016; Guilliams et al., 2016).”
Background
BDCA1+ cDC2s, BDCA2+ pDCs and BDCA3+ cDC1s reveal distinct pathophysiologic features and impact on clinical outcomes in melanoma patients
Cuevas, E. S., Ouaguia, L., Mouret, S., Charles, J., de Fraipont, F., Manches, O., Valladeau‐Guilemond, J., Bendriss‐Vermare, N., Chaperot, L., & Aspord, C. (2020) · Clinical & Translational Immunology · doi:10.1002/cti2.1190 · Cited by 32
“There are three functionally specialised main DC subsets in human peripheral blood and lymphoid tissues: conventional DCs (cDCs) segregated into type 2 cDCs (BDCA1/CD1c+ DCs, cDC2s) and type 1 cDCs (BDCA3/CD141 DCs, cDC1s), and plasmacytoid DCs (BDCA2 DCs, pDCs).(9,10) They differ in surface marker expression, localis…”
Background
CD300a and CD300f molecules regulate the function of leukocytes
Cao, Y., Ao, T., Wang, X., Wei, W., Fan, J., & Tian, X. (2021) · International Immunopharmacology · doi:10.1016/j.intimp.2021.107373 · Cited by 28
Human DC3 Antigen Presenting Dendritic Cells From Induced Pluripotent Stem Cells
Satoh, T., Toledo, M. A. S., Böhnke, J., Olschok, K., Flosdorf, N., Götz, K., Küstermann, C., Sontag, S., Seré, K., Koschmieder, S., et al. (2021) · Frontiers in Cell and Developmental Biology · doi:10.3389/fcell.2021.667304 · Cited by 29
“DC are classified into two main subsets, classical DC (cDC) and plasmacytoid DC (pDC), based on surface marker expression, function and ontogeny, and cDC are further subdivided into cDC1 and cDC2 (Guilliams et al., 2014; Mildner and Jung, 2014; Collin and Bigley, 2018; Amon et al., 2020).”
Background
SARS-CoV-2 Spike Protein and Its Receptor Binding Domain Promote a Proinflammatory Activation Profile on Human Dendritic Cells
Barreda, D., Santiago, C. A., Rodríguez, J. R., Rodrígúez, J. F., Casasnovas, J. M., Mérida, I., & Ávila‐Flores, A. (2021) · Cells · doi:10.3390/cells10123279 · Cited by 28
“S protein and RBD promote DCs maturation as shown by enhanced expression of MHC class I and II, which is in agreement with the phenotypic profile of mDCs [3].”
Result
Plasmacytoid Dendritic Cells as a Novel Cell-Based Cancer Immunotherapy
Hernández, S. S., Jakobsen, M. R., & Bak, R. O. (2022) · International Journal of Molecular Sciences · doi:10.3390/ijms231911397 · Cited by 28
“, expression of CD123, CD304, IGJ, and MZB1) [4,5,25].”
Background
Impact of disease-modifying therapy on dendritic cells and exploring their immunotherapeutic potential in multiple sclerosis
Liu, C., Zhu, J., Mi, Y., & Jin, T. (2022) · Journal of Neuroinflammation · doi:10.1186/s12974-022-02663-z · Cited by 29
“Maturing DCs undergo various changes, including: (a) the processing of phagocytosis antigens; (b) the elevated presentation of antigens on MHC class I and II molecules; (c) the increased expression of critical costimulatory molecules, such as CD40, CD80, and CD86; (d) the enhanced secretion of polarizing cytokines, su…”
Influential
The combination of gemcitabine and ginsenoside Rh2 enhances the immune function of dendritic cells against pancreatic cancer via the CARD9-BCL10-MALT1 / NF-κB pathway
Li, Q., He, J., Li, S., Tian, C., Yang, J., Yuan, H., Lu, Y. H., Fagone, P., Nicoletti, F., & Xiang, M. (2022) · Clinical Immunology · doi:10.1016/j.clim.2022.109217 · Cited by 28
Time-Course Transcriptomic Analysis Reveals the Crucial Roles of PANoptosis in Fungal Keratitis
Xu, X., Wei, Y., Pang, J., Wei, Z., Wang, L., Chen, Q., Wang, Z., Zhang, Y., Chen, K., Peng, Y., et al. (2023) · Investigative Ophthalmology & Visual Science · doi:10.1167/iovs.64.3.6 · Cited by 27
The Cellular Composition of the Uveal Immune Environment
Reekie, I. R., Sharma, S. M., Foers, A. D., Sherlock, J. P., Coles, M. C., Dick, A. D., Denniston, A. K., & Buckley, C. D. (2021) · Frontiers in Medicine · doi:10.3389/fmed.2021.721953 · Cited by 27
Shaping of Monocyte-Derived Dendritic Cell Development and Function by Environmental Factors in Rheumatoid Arthritis
Coutant, F. (2021) · International Journal of Molecular Sciences · doi:10.3390/ijms222413670 · Cited by 27
“currently used to characterize these DC subsets, such as CD141 and C-type lectin domain family 9 (CLEC9A) for cDC1; CD1c and CLEC10A for cDC2; CD123, CD303 and CD304 for pDC; CD1c and CD163 for DC3; AXL and SIGLEC6 for transitional DC [7].”
Method
Comprehensive Flow Cytometry Profiling of the Immune System in COVID-19 Convalescent Individuals
Gil-Manso, S., Blanco, I. M., López-Esteban, R., Carbonell, D., López-Fernández, L. A., West, L. J., Correa‐Rocha, R., & Pion, M. (2022) · Frontiers in Immunology · doi:10.3389/fimmu.2021.793142 · Cited by 30
“Nevertheless, it was reported that precursor myeloid cells could express CD123 (28, 29).”
BackgroundInfluential
Pathogenic role of monocytes/macrophages in large vessel vasculitis
Watanabe, R., & Hashimoto, M. (2022) · Frontiers in Immunology · doi:10.3389/fimmu.2022.859502 · Cited by 25
Dendritic Cells: The Long and Evolving Road towards Successful Targetability in Cancer
Marmonti, E., Oliva, J., & Haymaker, C. (2022) · Cells · doi:10.3390/cells11193028 · Cited by 29
How cell migration helps immune sentinels
Delgado, M., & Lennon‐Duménil, A. (2022) · Frontiers in Cell and Developmental Biology · doi:10.3389/fcell.2022.932472 · Cited by 27
“lymphocytes and some myeloid cells (DCs and tissue-resident macrophages) exhibit an amoeboid motility (von Andrian and Mempel 2003; Lämmermann et al., 2008; Jacobelli et al., 2010; Collin and Bigley 2018).”
Background
Counteracting Immunosenescence—Which Therapeutic Strategies Are Promising?
Hieber, C., Grabbe, S., & Bros, M. (2023) · Biomolecules · doi:10.3390/biom13071085 · Cited by 30
“Whereas cDCs produce IL-12 and activate helper T cells (Th)1, pDCs express surface markers of both myeloid and lymphoid origin and secrete interferon (IFN)α/β in response to (viral) infection [90,91].”
Background
B-cells in pulmonary arterial hypertension: friend, foe or bystander?
Sanges, S., Tian, W., Dubucquoi, S., Chang, J., Collet, A., Launay, D., & Nicolls, M. R. (2024) · European Respiratory Journal · doi:10.1183/13993003.01949-2023 · Cited by 26
“Aside from follicular dendritic cells, which operate within germinal centres in cooperation with Tfh cells, other DC subsets, such as conventional dendritic cells and monocyte-derived dendritic cells (moDCs), have been implicated in both T-cell and B-cell priming and activation [36].”
Background
Microbial Symphony: Exploring the Role of the Gut in Osteoarthritis-Related Pain. A Narrative Review
Corriero, A., Giglio, M., Soloperto, R., Inchingolo, F., Varrassi, G., & Puntillo, F. (2024) · Pain and Therapy · doi:10.1007/s40122-024-00602-9 · Cited by 28
“They link the innate and adaptive immune systems by recognizing and responding to PAMP and DAMP [43].”
Background
ZBTB46 coordinates angiogenesis and immunity to control tumor outcome
Kabir, A. U., Zeng, C., Subramanian, M., Wu, J., Kim, M., Krchma, K., Wang, X., Halabi, C. M., Pan, H., Wickline, S. A., et al. (2024) · Nature Immunology · doi:10.1038/s41590-024-01936-4 · Cited by 26
Formulation and evaluation of PVA-based composite hydrogels: physicochemical, leachables, and in vitro immunogenicity studies
Himawan, A., Korelidou, A., Pérez‐Moreno, A. M., Paris, J. L., Domínguez‐Robles, J., Vora, L. K., Permana, A. D., Larrañeta, E., Graham, R., Scott, C. J., et al. (2025) · Journal of Materials Chemistry B · doi:10.1039/d4tb02181a · Cited by 28
Severe respiratory syncytial virus disease in preterm infants: a case of innate immaturity
Anderson, J., Do, L. A. H., Wurzel, D. F., Toh, Z. Q., Mulholland, K., Pellicci, D. G., & Licciardi, P. V. (2021) · Thorax · doi:10.1136/thoraxjnl-2020-216291 · Cited by 27
Inhibition of Dendritic Cell Activation and Modulation of T Cell Polarization by the Platelet Secretome
Saris, A., Steuten, J., Schrijver, D. P., van Schijndel, G. M. W., Zwaginga, J. J., van Ham, S. M., & ten Brinke, A. (2021) · Frontiers in Immunology · doi:10.3389/fimmu.2021.631285 · Cited by 26
“As myeloid cDC2s have an extensive array of PRRs and a widespread tissue distribution, platelet-mediated inhibition could affect immunity against a wide range of pathogens (32).”
Clinically applicable CD34+-derived blood dendritic cell subsets exhibit key subset-specific features and potently boost anti-tumor T and NK cell responses
van der Sluijs, J. V. E., van Ens, D., Thordardottir, S., Vodegel, D., Hermens, I. A. T., van der Waart, A. B., Falkenburg, J. H. F., Kester, M. G. D., de Rink, I., Heemskerk, M. H. M., et al. (2021) · Cancer Immunology Immunotherapy · doi:10.1007/s00262-021-02899-3 · Cited by 27
“These CD34+ HPC-derived DC subsets were identified within total cultured cells using conventional markers: CD123+CD303+ pDCs, HLA-DR+CD1c+ cDC2s and CD141+CLEC9A+ cDC1s (Fig.”
BackgroundInfluential
Argon Plasma Exposure Augments Costimulatory Ligands and Cytokine Release in Human Monocyte-Derived Dendritic Cells
Bekeschus, S., Meyer, D., Arlt, K., von Woedtke, T., Miebach, L., Freund, E., & Clemen, R. (2021) · International Journal of Molecular Sciences · doi:10.3390/ijms22073790 · Cited by 26
Protective Effect of Saffron in Mouse Colitis Models Through Immune Modulation
Singh, G., Haileselassie, Y., Ji, A. R., Maecker, H. T., Sinha, S. R., Brim, H., Habtezion, A., & Ashktorab, H. (2021) · Digestive Diseases and Sciences · doi:10.1007/s10620-021-07163-3 · Cited by 26
Sepsis Inflammation Impairs the Generation of Functional Dendritic Cells by Targeting Their Progenitors
Lu, J., Sun, K., Yang, H., Fan, D., Huang, H., Hong, Y., Wu, S., Zhou, H., Fang, F., Li, Y., et al. (2021) · Frontiers in Immunology · doi:10.3389/fimmu.2021.732612 · Cited by 26
Peripheral immune cells in NAFLD patients: A spyhole to disease progression
Lin, S., & Fan, J. (2021) · EBioMedicine · doi:10.1016/j.ebiom.2021.103768 · Cited by 26
Respiratory and systemic monocytes, dendritic cells, and myeloid‐derived suppressor cells in COVID‐19: Implications for disease severity
Falck‐Jones, S., Österberg, B., & Smed‐Sörensen, A. (2022) · Journal of Internal Medicine · doi:10.1111/joim.13559 · Cited by 27
Research progress on the active ingredients of traditional Chinese medicine in the intervention of atherosclerosis: A promising natural immunotherapeutic adjuvant
Jing, J., Zhu, C., Gong, R., Qi, X., Zhang, Y., & Zhang, Z. (2023) · Biomedicine & Pharmacotherapy · doi:10.1016/j.biopha.2022.114201 · Cited by 27
Major alterations to monocyte and dendritic cell subsets lasting more than 6 months after hospitalization for COVID-19
Hopkins, F. R., Govender, M., Svanberg, C., Nordgren, J., Waller, H., Nilsdotter‐Augustinsson, Å., Henningsson, A. J., Hagbom, M., Sjöwall, J., Nyström, S. N., et al. (2023) · Frontiers in Immunology · doi:10.3389/fimmu.2022.1082912 · Cited by 26
Systemic Alterations in Type-2 Conventional Dendritic Cells Lead to Impaired Tumor Immunity in Pancreatic Cancer
James, C. A., Baer, J. M., Zou, C., Panni, U. Y., Knolhoff, B. L., Hogg, G. D., Kingston, N. L., Kang, L., Lander, V. E., Luo, J. R., et al. (2023) · Cancer Immunology Research · doi:10.1158/2326-6066.cir-21-0946 · Cited by 26
When the allergy alarm bells toll: The role of Toll-like receptors in allergic diseases and treatment
Wenger, M., Grosse-Kathoefer, S., Kraiem, A., Pelamatti, E., Nunes, N. N. D. S., Pointner, L., & Aglas, L. (2023) · Frontiers in Molecular Biosciences · doi:10.3389/fmolb.2023.1204025 · Cited by 31
“In vitro generated monocyte-derived dendritic cells (moDCs) are commonly used, although they do not fully resemble myeloid DCs in the blood (Collin and Bigley, 2018).”
Background
Impact of Plasma Membrane Domains on IgG Fc Receptor Function
Kara, S., Amon, L., Lühr, J. J., Nimmerjahn, F., Dudziak, D., & Lux, A. (2020) · Frontiers in Immunology · doi:10.3389/fimmu.2020.01320 · Cited by 29
Effects of Neuropeptides on Dendritic Cells in the Pathogenesis of Psoriasis
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Dendritic Cells: Neglected Modulators of Peripheral Immune Responses and Neuroinflammation in Mood Disorders?
Dantas, R. L., Freff, J., Ambrée, O., Beins, E. C., Forstner, A. J., Dannlowski, U., Baune, B. T., Scheu, S., & Alferink, J. (2021) · Cells · doi:10.3390/cells10040941 · Cited by 29
“In humans, they can be found in lymphoid tissues, lung, and peripheral blood [79].”
BackgroundInfluential
Co-Infection and Cancer: Host–Pathogen Interaction between Dendritic Cells and HIV-1, HTLV-1, and Other Oncogenic Viruses
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“Accordingly, the major subsets of DCs include myeloid/conventional DC1 (cDC1), myeloid/conventional DC2 (cDC2), and plasmacytoid DC (pDC) [11].”
Background
Predicting diagnostic gene expression profiles associated with immune infiltration in patients with lupus nephritis
Wang, L., Yang, Z., Yu, H., Lin, W., Wu, R., Yang, H., & Yang, K. (2022) · Frontiers in Immunology · doi:10.3389/fimmu.2022.839197 · Cited by 25
Microenvironment-responsive nanosystems for osteoarthritis therapy
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Developing Human Skin Contains Lymphocytes Demonstrating a Memory Signature
Dhariwala, M. O., Karthikeyan, D., Vasquez, K. S., Farhat, S., Weckel, A., Taravati, K., Leitner, E. G., Clancy, S., Pauli, M. L., Piper, M. L., et al. (2020) · Cell Reports Medicine · doi:10.1016/j.xcrm.2020.100132 · Cited by 26
“21,22 25 Deﬁnitive assignment of clusters 16 and 17, which were enriched in fetal as compared to adult skin, was precluded by the absence of subset-deﬁning markers.”
Human Peripheral Blood Dendritic Cell and T Cell Activation by Codium fragile Polysaccharide
Zhang, W., Hwang, J., Park, H., Lim, S.-M., Go, S., Kim, J., Choi, I., You, S., & Jin, J. (2020) · Marine Drugs · doi:10.3390/md18110535 · Cited by 25
“DCs are the most powerful antigen-presenting cells that induce T cell immunity [17,18].”
Background
The BTLA–HVEM–CD5 Immunoregulatory Axis–An Instructive Mechanism Governing pTreg Cell Differentiation
Bourque, J., & Hawiger, D. (2019) · Frontiers in Immunology · doi:10.3389/fimmu.2019.01163 · Cited by 26
Single cell RNA-Seq reveals pre-cDCs fate determined by transcription factor combinatorial dose
Ma, W., Lee, J., Backenroth, D., Zhou, Y. J., Bush, E. C., Sims, P. A., Liu, K., & Shen, Y. (2019) · BMC Molecular and Cell Biology · doi:10.1186/s12860-019-0199-y · Cited by 24

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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