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Human dendritic cell subsets: an update
Open accessAbstract
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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“The three other proteins increased in abundance in TET2-CH were CD1C (a marker of conventional dendritic cells), CLEC4C (a marker of plasmacytoid dendritic cells) and CD86 (a marker of dendritic cells, monocytes and other antigen-presenting cells)51.”
From Rare variant associations with plasma protein levels in the UK Biobank (2023) · cites this paper as [51]
Experimental — accuracy not yet measuredIn the citing paper
“pDCs are instead characterized by a marked impairment of cytokine release in older people (27, 29).”
From Immunosenescence and Its Hallmarks: How to Oppose Aging Strategically? A Review of Potential Options for Therapeutic Intervention (2019) · cites this paper as [27]
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“However, whether this is truly a cDC population or instead moDCs might be the question since CD141, and CD1c, previously used to describe cDCs are also expressed by moDC [75].”
BackgroundInfluentialGeldhof, V., de Rooij, L. P. M. H., Sokol, L., Amersfoort, J., Schepper, M. D., Rohlenová, K., Hoste, G., Vanderstichele, A., Delsupehe, A.-M., Isnaldi, E., et al. (2022) · Nature Communications · doi:10.1038/s41467-022-33052-y · Cited by 145
Wculek, S. K., Amores, J., Conde‐Garrosa, R., Khouili, S. C., Melero, I., & Sancho, D. (2019) · Journal for ImmunoTherapy of Cancer · doi:10.1186/s40425-019-0565-5 · Cited by 143
Dexosomes as a cell-free vaccine for cancer immunotherapy
Nikfarjam, S., Rezaie, J., Kashanchi, F., & Jafari, R. (2020) · Journal of Experimental & Clinical Cancer Research · doi:10.1186/s13046-020-01781-x · Cited by 148
“Conventional DCs (cDCs), plasmacytoid DCs (pDCs) and monocyte-derived DCs (moDCs) comprise the three classic subsets of DCs in human [8, 9].”
BackgroundRegulatory Dendritic Cells, T Cell Tolerance, and Dendritic Cell Therapy for Immunologic Disease
Ness, S., Lin, S., & Gordon, J. (2021) · Frontiers in Immunology · doi:10.3389/fimmu.2021.633436 · Cited by 138
Emile, J., Aubart, F. C., Collin, M. P., Fraitag, S., Idbaïh, A., Abdel-Wahab, O. I., Rollins, B. J., Donadieu, J., & Haroche, J. (2021) · The Lancet · doi:10.1016/s0140-6736(21)00311-1 · Cited by 138
CD4+ T cells in antitumor immunity
Montauti, E. I., Oh, D. Y., & Fong, L. H. (2024) · Trends in cancer · doi:10.1016/j.trecan.2024.07.009 · Cited by 154
Osteoinduction and osteoimmunology: Emerging concepts
Miron, R. J., Bohner, M., Zhang, Y., & Bosshardt, D. D. (2023) · Periodontology 2000 · doi:10.1111/prd.12519 · Cited by 143
Immune System Evasion as Hallmark of Melanoma Progression: The Role of Dendritic Cells
Tucci, M., Passarelli, A. M., Mannavola, F., Felici, C., Stucci, L. S., Cives, M., & Silvestris, F. (2019) · Frontiers in Oncology · doi:10.3389/fonc.2019.01148 · Cited by 139
Trial watch: Dendritic cell (DC)-based immunotherapy for cancer
Laureano, R. S., Sprooten, J., Vanmeerbeerk, I., Borràs, D., Govaerts, J., Naulaerts, S., Berneman, Z. N., Beuselinck, B., Bol, K. F., Borst, J. G., et al. (2022) · OncoImmunology · doi:10.1080/2162402x.2022.2096363 · Cited by 134
mRNA as novel technology for passive immunotherapy
Schlake, T., Theß, A., Thran, M., & Jordan, I. (2018) · Cellular and Molecular Life Sciences · doi:10.1007/s00018-018-2935-4 · Cited by 135
“Dendritic cells (DCs) process and present antigen for the transition from innate to adaptive immunity [7].”
BackgroundMajor alterations in the mononuclear phagocyte landscape associated with COVID-19 severity
Kvedaraite, E., Hertwig, L., Sinha, I., Ponzetta, A., Myrberg, I. H., Lourda, M., Dzidic, M., Akber, M., Klingström, J., Folkesson, E., et al. (2021) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.2018587118 · Cited by 128
“Among cDCs, cDC1s are specialized in cross-presenting antigens to CD8 T cells while cDC2s initiate T-helper cell responses, both of which are essential for successful viral clearance (12).”
BackgroundBeyond cDC1: Emerging Roles of DC Crosstalk in Cancer Immunity
Noubade, R., Majri-Morrison, S. S., & Tarbell, K. V. (2019) · Frontiers in Immunology · doi:10.3389/fimmu.2019.01014 · Cited by 134
Huber, A., Dammeijer, F. F., Aerts, J. G. J. V., & Vroman, H. H. (2018) · Frontiers in Immunology · doi:10.3389/fimmu.2018.02804 · Cited by 128
Mpakali, A., & Stratikos, E. (2021) · Cancers · doi:10.3390/cancers13010134 · Cited by 130
Specialized immune responses in the peritoneal cavity and omentum
Liu, M., Silva-Sánchez, A., Randall, T. D., & Meza‐Perez, S. (2020) · Journal of Leukocyte Biology · doi:10.1002/jlb.5mir0720-271rr · Cited by 135
Multimodel preclinical platform predicts clinical response of melanoma to immunotherapy
Pérez‐Guijarro, E., Yang, H. H., Araya, R. E., Meskini, R. E., Michael, H. T., Vodnala, S. K., Marie, K. L., Smith, C., Chin, S., Lam, K. C., et al. (2020) · Nature Medicine · doi:10.1038/s41591-020-0818-3 · Cited by 119
Single-cell map of diverse immune phenotypes in the acute myeloid leukemia microenvironment
Guo, R., Lü, M., Cao, F., Wu, G., Gao, F., Pang, H., Li, Y., Zhang, Y., Xing, H., Liang, C., et al. (2021) · Biomarker Research · doi:10.1186/s40364-021-00265-0 · Cited by 116
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Ex vivo pulsed dendritic cell vaccination against cancer
Gu, Y., Zhao, X., & Song, X. (2020) · Acta Pharmacologica Sinica · doi:10.1038/s41401-020-0415-5 · Cited by 115
Wenzek, C., Boelen, A., Westendorf, A. M., Engel, D. R., Moeller, L. C., & Führer-Sakel, D. (2022) · European Journal of Endocrinology · doi:10.1530/eje-21-1171 · Cited by 125
C-Type Lectin Receptors in Host Defense Against Bacterial Pathogens
Mnich, M. E., van Dalen, R., & van Sorge, N. M. (2020) · Frontiers in Cellular and Infection Microbiology · doi:10.3389/fcimb.2020.00309 · Cited by 112
“induce APC tissue adaptation, resulting in different receptor expression profiles and migratory capacities of similar APC subtypes in different tissues (Lundberg et al., 2013; AlcantaraHernandez et al., 2017; Collin and Bigley, 2018).”
BackgroundType I Interferon Production of Plasmacytoid Dendritic Cells under Control
Bencze, D., Fekete, T., & Pázmándi, K. (2021) · International Journal of Molecular Sciences · doi:10.3390/ijms22084190 · Cited by 117
Zhu, T., Han, J., Liu, Y., Cai, Z., Sun, W. Y., Hua, Y., & Xu, J. (2022) · Frontiers in Immunology · doi:10.3389/fimmu.2022.907550 · Cited by 113
“DCs act as a bridge between innate and adaptive immunity and are the most important antigen-presenting cells (65).”
BackgroundMoving on From Sipuleucel-T: New Dendritic Cell Vaccine Strategies for Prostate Cancer
Sutherland, S., Ju, X., Horvath, L. G., & Clark, G. J. (2021) · Frontiers in Immunology · doi:10.3389/fimmu.2021.641307 · Cited by 115
Hadler‐Olsen, E., & Wirsing, A. M. (2019) · British Journal of Cancer · doi:10.1038/s41416-019-0409-6 · Cited by 109
Qin, L., Zhang, H., Zhou, Y., Umeshappa, C. S., & Gao, H. (2021) · Small · doi:10.1002/smll.202006000 · Cited by 110
Vaccine adjuvants to engage the cross-presentation pathway
Lee, W., & Suresh, M. (2022) · Frontiers in Immunology · doi:10.3389/fimmu.2022.940047 · Cited by 106
Cline-Smith, A., Axelbaum, A., Shashkova, E., Chakraborty, M., Sanford, J., Panesar, P., Peterson, M., Cox, L., Baldan, A., Veis, D., et al. (2020) · Journal of Bone and Mineral Research · doi:10.1002/jbmr.3966 · Cited by 108
cGAS-STING pathway mediates activation of dendritic cell sensing of immunogenic tumors
Li, G., Zhao, X., Zheng, Z., Zhang, H., Wu, Y., Shen, Y., & Chen, Q. (2024) · Cellular and Molecular Life Sciences · doi:10.1007/s00018-024-05191-6 · Cited by 114
Integrated analysis of multimodal single-cell data with structural similarity
Cao, Y., Fu, L., Wu, J., Peng, Q., Nie, Q. H., Zhang, J., & Xie, X. S. (2022) · Nucleic Acids Research · doi:10.1093/nar/gkac781 · Cited by 109
“We validate these ground truth cell type labels by visualizing some enriched expressions of known cell type-specific marker genes (Figure S2), such as pDC cells (with known marker genes CLEC4C and NRP1) (44–47), and Treg cells (with known marker gene FOXP3 and RTKN2) (48,49).”
Srivastava, S., Jackson, C., Kim, T., Choi, J. H., & Lim, M. K. (2019) · Cancers · doi:10.3390/cancers11040537 · Cited by 105
“They are known as myeloid DC (mDCs), conventional DCs, or classic DCs (cDCs) and express CD141 and CD1c [42,43]. pDCs are derived from both committed myeloid and lymphoid precursors and are known to express CD123 and CD303 [43–45].”
BackgroundCalmeiro, J., Carrascal, M. A., Tavares, A. R., Ferreira, D. A., Gomes, C. M. F., Falcão, A. C., Cruz, M. T., & Neves, B. M. (2020) · Pharmaceutics · doi:10.3390/pharmaceutics12020158 · Cited by 107
“Human DCs develop from multipotent hematopoietic stem cells (HSCs) primed by predestined-related but distinct pathways of lympho-myeloid hematopoiesis, which share a common transitory phenotype and differentiate into specific subsets by the influence of lineage-specific transcription factors, particularly IRF8 and IRF…”
BackgroundInfluentialMycobacterium tuberculosis : immune response, biomarkers, and therapeutic intervention
Li, Z., Yang, L., Li, L., Ye, Z., & Gong, W. (2024) · MedComm · doi:10.1002/mco2.419 · Cited by 123
“54 DCs are widely distributed in human tissues, except for the brain, and can be classified into immature DCs (iDCs) and mature DCs (mDCs) based on their stage of development.”
BackgroundNew Insights of CCR7 Signaling in Dendritic Cell Migration and Inflammatory Diseases
Hong, W., Yang, B., He, Q., Wang, J., & Weng, Q. (2022) · Frontiers in Pharmacology · doi:10.3389/fphar.2022.841687 · Cited by 105
“DCs mainly incorporate “conventional” or “classical” DCs (cDCs) and plasmacytoid DCs (pDCs) (Worbs et al., 2017; Collin and Bigley, 2018).”
Background
Metadata
- Authors
- Collin, M., & Bigley, V.
- Affiliations
- Newcastle upon Tyne Hospitals NHS Foundation Trust (GB)
- Corresponding author
- Collin, Matthew
- Venue
- Immunology
- Publisher
- Wiley
- Published
- 2018-02-27
- Volume
- 154
- Issue
- 1
- Pages
- 3-20
- ISSN
- 0019-2805 (ISSN-L)
- 1365-2567
- 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
- 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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