A Guide to Dendritic Cell Markers

Dendritic cells (DC) are bone marrow-derived immune cells that can be found in the blood, lymphoid organs, and various tissues in the body. They are generally stellate in morphology, with branching dendrites that resemble those of neurons. DCs are multipurpose players in the immune system, serving as mobile messengers that can carry out innate and adaptive immune functions. Among their innate immune roles, DCs can recognize and respond to pathogen‐associated and danger‐associated signals. From phagocytosing pathogens, DCs can absorb and present antigens. Activated DCs will then migrate into lymph nodes to interact with T cells and B cells, directly influencing adaptive immunity. DCs also play roles in inflammation, as well as in cancer progression, highlighting more potential applications in therapeutics. Much work has been done in trying to fully understand the complexities and diversity of dendritic cell populations in mice and humans. In this article, we will review the major dendritic cell subpopulations and their associated protein markers.

Markers for dendritic cell precursors

In the classical model of dendritic cell (DC) development, hematopoietic stem cells in the bone marrow give rise to macrophage and DC precursors (MDPs). Cells not destined to become monocytes or macrophages will differentiate into common DC precursors (CDPs). From this subset, pre-DCs will exit the bone marrow and migrate to lymphoid and non-lymphoid tissue to mature into conventional DCs (cDCs). FLT3 has been reported to be a marker for MDP, CDP, pre-DCs. Other markers include CX3CR1 (MDP), CSF1R (CDP), and  ITGAX (pre-DC). It should be noted that more recent research suggests that each DC progenitor could follow a predestined pathway beginning at early development, as opposed to a series of fate decisions occurring at the MDP and CDP stages.

Image: This diagram highlights prominent dendritic cell subsets, including common cell markers.

Markers for conventional dendritic cells

The conventional DC (cDC), sometimes also referred to as classical DC or myeloid DC, travels through the blood to differentiate within lymphoid and non-lymphoid tissues. This DC subset features irregularly-shaped cells with many cell membrane processes. In particular, they are known to be specialized for absorbing antigens for presentation to naïve T cells in adaptive immunity. cDCs are further categorized into two major subpopulations, cDC1 and cDC2.

cDC1 — Mouse and human cDC1 have been found to excel in cross-presentation and are effective in priming CD8+ T cells against extracellular antigens such as those of bacteria and viruses. They are known to secrete interleukin-12, as well as type I and type III interferons, and are believed to promote Th1 helper T cell and natural killer responses. Human cDC1s are also reported to be efficient in presenting necrotic antigens to T cells, partly due to the binding of CLEC9A to the exposed actin of necrotic cells. The cDC1 subset appears to be important in antitumor immunity and is correlated with beneficial prognosis in cancer. Prominent cDC1 markers include CD8A, CLEC9A, ITGAE, ITGAX, THBD (CD141), and XCR1.

cDC2 — cDC2s are a dominant subset of DCs residing in the blood, tissues, and lymphoid organs. They express a wide repertoire of pattern recognition receptors, including Toll-like receptors and lectins, that drive innate immune responses. They have been shown to induce Th2 and Th17 helper T cell responses and a role in inducing of CD4+ T cell response has been suggested. cDC2s appear to have many regulatory roles, such as inducing regulatory T cells in the intestine and maintaining tolerance in the liver. Human cDC2s are understood to be heterogeneous and have been recently suggested to include more distinct subtypes. Commonly mentioned cDC2 markers include CD1C, CD207, ITGAM, NOTCH2, and SIRPA.

Markers for plasmacytoid dendritic cells

Use Biocompare’s Antibody Search Tool
Find and compare antibodies
from different suppliers Search

Plasmacytoid dendritic cells (pDCs) mature directly from CDPs within the bone marrow before migrating to the blood and peripheral lymphoid tissues. These round, plasma cell-shaped cells are less abundant than their conventional counterparts. pDCs are notable for being able to rapidly produce type I and type III interferons and cytokines, making this an important subset for responding to acute or chronic viral infection. pDCs express MHC II, potentially being able to act as antigen-presenting cells. Subsets also exist among the pDCs. One population, defined by high expression of CD2, has been found to exclusively induce CD4+ T cell proliferation. Upon stimulation, pDCs have been reported to also activate CD8+ T cells. Markers for pDCs include CLEC4C, LILRB4, NRP1, CCR7, B220 (mouse), and SiglecH (mouse). 

Markers for other dendritic cell types

Monocyte-derived dendritic cells (mo-DC) — In earlier in vitro studies of dendritic cells, monocytes could be stimulated with certain factors to differentiate into dendritic cells. However, it is now believed that a subset of inflammatory DCs can arise from monocytes that are recruited from the blood to tissues during times of inflammation. This subset, while featuring a dendritic morphology, also shares gene signatures of the in vitro monocyte-derived DCs (mo-DCs). While this subset’s identity may still require further clarification, there is a general understanding that the mo-DC is produced in response to inflammation and that this subset promotes CD4+ T cells to produce a Th17 immune response. Some markers reported for mo-DCs include CD14, MRC1 (CD206), CD209, SIRPA, ITGAM (CD11b), and CD1A.

Langerhans cells (LC) — LC are immune cells residing in areas of stratified squamous epithelium, such as the skin. They are macrophages in origin but have also been considered to be dendritic cell-like due to phenotype. Like dendritic cells, LC can extend dendrites, absorb foreign antigens, travel to the lymph node, and then present the antigen to T cells. Langherans markers include CD1A, CD207 (Langerin), and ID2.

AXL+Siglec6+ dendritic cells (AS DC) — A population of pre-DC in the blood appears to form a distinct, functional subset that is distinct from pDCs and cDCs. Identified by the expression of two key markers, AXL and Siglec6 (CD327), this subset is reported to strongly stimulate T cells in lymphoid tissue. It is noted that AS DCs may also be a mature cDC2s precursor and may potentially transition toward this subset.

Table of Dendritic Cell Markers

The table below lists human genes (or proteins*) that have been described as DC markers in recent literature. A majority listed are membrane markers expressed on the cell surface. Also included are other defining proteins, including transcription factors and signaling proteins, such as cytokines. Accompanying each marker are links to relevant antibodies and ELISA kits, as these immunodetection tools are routinely used in cell characterization studies via flow cytometry and immunostaining. The associated products are offered by a variety of manufacturers and can serve as a useful reference for dendritic cell immunodetection. 

Note: *Some proteins are protein isoforms or multi-subunit protein complexes composed of several distinct genes. Information on Protein Type, Localization, and Size (kDa) obtained from UniProt.org.

References

1. Schraml BU, Reis e Sousa C. Defining dendritic cells. Curr Opin Immunol. 2015;32:13-20. doi:10.1016/j.coi.2014.11.001
2. Collin M, Bigley V. Human dendritic cell subsets: an update. Immunology. 2018;154(1):3-20. doi:10.1111/imm.12888
3. Schlitzer A, Zhang W, Song M, Ma X. Recent advances in understanding dendritic cell development, classification, and phenotype. F1000Res. 2018;7:F1000 Faculty Rev-1558. Published 2018 Sep 26. doi:10.12688/f1000research.14793.1
4. Mair, F. and Prlic, M. (2018), OMIP‐044: 28‐color immunophenotyping of the human dendritic cell compartment. Cytometry, 93: 402-405. https://doi.org/10.1002/cyto.a.23331
5. Rhodes JW, Tong O, Harman AN, Turville SG. Human Dendritic Cell Subsets, Ontogeny, and Impact on HIV Infection. Front Immunol. 2019;10:1088. Published 2019 May 16. doi:10.3389/fimmu.2019.01088
6. Patente TA, Pinho MP, Oliveira AA, Evangelista GCM, Bergami-Santos PC, Barbuto JAM. Human Dendritic Cells: Their Heterogeneity and Clinical Application Potential in Cancer Immunotherapy. Front Immunol. 2019;9:3176. Published 2019 Jan 21. doi:10.3389/fimmu.2018.03176
7. Wculek, S.K., Cueto, F.J., Mujal, A.M. et al. Dendritic cells in cancer immunology and immunotherapy. Nat Rev Immunol 20, 7–24 (2020). https://doi.org/10.1038/s41577-019-0210-z