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  • Print publication year: 2007
  • Online publication date: August 2009

1 - Subpopulations and differentiation of mouse dendritic cells

from I - Dendritic cells and their role in immunity



Dendritic cells (DCs) have an essential function in the immune system by participating in primitive defense responses that constitute the innate immunity, as well as in the induction and regulation of antigen-specific immune responses. This allows DCs to control infections caused by parasitic and microbial pathogens, to block tumour growth and to exert a precise regulation of T cell, B cell and NK cell immune responses. In addition, DCs also fulfill a pivotal role in the induction and maintenance of T cell tolerance. The functional diversity characterizing the DC system relies essentially on the remarkable plasticity of the DC differentiation process, which dictates the acquisition of DC functional specialization through the generation of a large collection of DC subpopulations (reviewed by Shortman and Liu, 2002). Dendritic cells are located both in the lymphoid organs (such as the spleen or the lymph nodes), and in non-lymphoid tissues (such as the skin or the liver), and can be classified in two major categories: conventional DCs (cDCs), and plasmacytoid DCs (pDCs). Whereas in turn cDCs comprise multiple DC subpopulations endowed with specific functions, little is known about the functional heterogeneity of pDCs. A summary of the most relevant phenotypic and functional characteristics of the main DC subpopulations present in mice is shown in Table 1.1.

A first group of cDCs includes those that are common, and largely restricted, to the majority of organized lymphoid organs of the immune system, and perform their specific functions, as immature or mature DCs, within these organs.

Aliberti, J., Sousa, C. Reis e, Schito, M., Hieny, S., Wells, T., Huffnagle, G. B. and Sher, A. (2000). CCR5 provides a signal for microbial induced production of interleukin-12 by CD8 alpha+ dendritic cells. Nat. Immunol., 1, 83–7
Aliberti, J., Schulz, O., Pennington, D. J., Tsujimura, H., Sousa, C. Reis e, Ozato, K. and Sher, A. (2003). Essential role for ICSBP in the in vivo development of murine CD8alpha+ dendritic cells. Blood, 101, 305–10
Allan, R. S., Smith, C. M., Belz, G. T., Lint, A. L., Wakim, L. M., Heath, W. R. and Carbone, F. R. (2003). Epidermal viral immunity induced by CD8alpha+ dendritic cells but not by Langerhans cells. Science, 301, 1925–8
Ardavín, C. (1997). Thymic dendritic cells. Immunol Today, 18, 350–61
Ardavín, C. (2003). Origin, precursors and differentiation of mouse dendritic cells. Nat. Rev. Immunol., 3, 582–90
Ardavín, C., Wu, L., Li, C. L. and Shortman, K. (1993). Thymic dendritic cells and T cells develop simultaneously in the thymus from a common precursor population. Nature, 362, 761–3
Asselin-Paturel, C., Brizard, G., Pin, J. J., Briere, F. and Trinchieri, G. (2003). Mouse strain differences in plasmacytoid dendritic cell frequency and function revealed by a novel monoclonal antibody. J. Immunol., 171, 6466–77
Barchet, W., Cella, M., Odermatt, B., Asselin-Paturel, C., Colonna, M. and Kalinke, U. (2002). Virus-induced interferon alpha production by a dendritic cell subset in the absence of feedback signaling in vivo. J. Exp. Med., 195, 507–16
Barchet, W., Cella, M. and Colonna, M. (2005). Plasmacytoid dendritic cells-virus experts of innate immunity. Semin. Immunol., 17, 253–61
Belz, G. T., Behrens, G. M., Smith, C. M., Miller, J. F., Jones, C., Lejon, K., Fathman, C. G., Mueller, S. N., Shortman, K., Carbone, F. R. and Heath, W. R. (2002). The CD8alpha(+) dendritic cell is responsible for inducing peripheral self-tolerance to tissue-associated antigens. J. Exp. Med., 196, 1099–104
Belz, G. T., Smith, C. M., Kleinert, L., Reading, P., Brooks, A., Shortman, K., Carbone, F. R. and Heath, W. R. (2004). Distinct migrating and nonmigrating dendritic cell populations are involved in major histocompatibility complex class I-restricted antigen presentation after lung infection with virus. Proc. Natl Acad. Sci. U S A, 101, 8670–5
Belz, G. T., Shortman, K., Bevan, M. J. and Heath, W. R. (2005). CD8alpha+ dendritic cells selectively present major histocompatibility complex class I-restricted noncytolytic viral and intracellular bacterial antigens in vivo. J. Immunol., 175, 196–200
Benvenuti, F., Hugues, S., Walmsley, M., Ruf, S., Fetler, L., Popoff, M., Tybulewicz, V. L. and Amigorena, S. (2004). Requirement of Rac1 and Rac2 expression by mature dendritic cells for T cell priming. Science, 305, 1150–3
Blasius, A., Vermi, W., Krug, A., Facchetti, F., Cella, M. and Colonna, M. (2004). A cell-surface molecule selectively expressed on murine natural interferon-producing cells that blocks secretion of interferon-alpha. Blood, 103, 4201–6
Borkowski, T. A., Letterio, J. J., Farr, A. G. and Udey, M. C. (1996). A role for endogenous transforming growth factor beta 1 in Langerhans cell biology: the skin of transforming growth factor beta 1 null mice is devoid of epidermal Langerhans cells. J. Exp. Med., 184, 2417–22
Chicha, L., Jarrossay, D. and Manz, M. G. (2004). Clonal type I interferon-producing and dendritic cell precursors are contained in both human lymphoid and myeloid progenitor populations. J. Exp. Med., 200, 1519–24
Colonna, M., Trinchieri, G. and Liu, Y. J. (2004). Plasmacytoid dendritic cells in immunity. Nat. Immunol., 5, 1219–26
D'Amico, A. and Wu, L. (2003). The early progenitors of mouse dendritic cells and plasmacytoid predendritic cells are within the bone marrow hemopoietic precursors expressing Flt3. J. Exp. Med., 198, 293–303
Daro, E., Pulendran, B., Brasel, K., Teepe, M., Pettit, D., Lynch, D. H., Vremec, D., Robb, L., Shortman, K., McKenna, H. J., Maliszewski, C. R. and Maraskovsky, E. (2000). Polyethylene glycol-modified granulocyte-macrophage colony-stimulating factor expands CD11b(high)CD11c(high) but not CD11b(low)CD11c(high) murine dendritic cells in vivo: a comparative analysis with Flt3 ligand. J. Immunol., 165, 49–58
Smedt, T., Pajak, B., Muraille, E., Lespagnard, L., Heinen, E., Baetselier, P., Urbain, J., Leo, O. and Moser, M. (1996). Regulation of dendritic cell numbers and maturation by lipopolysaccharide in vivo. J. Exp. Med., 184, 1413–24
Haan, J. M., Lehar, S. M. and Bevan, M. J. (2000). CD8(+) but not CD8(−) dendritic cells cross-prime cytotoxic T cells in vivo. J. Exp. Med., 192, 1685–96
Edwards, A. D., Diebold, S. S., Slack, E. M., Tomizawa, H., Hemmi, H., Kaisho, T., Akira, S. and Sousa, C. Reis e (2003). Toll-like receptor expression in murine dendritic cell subsets: lack of Toll-like receptor7 expression by CD8 alpha+ dendritic cell correlates with unresponsiveness to imidazoquinolines. Eur. J. Immunol., 33, 827–33
Fallarino, F., Grohmann, U., Vacca, C., Bianchi, R., Fioretti, M. C. and Puccetti, P. (2002). CD40 ligand and cytotoxic T lymphocytesA-4 are reciprocally regulated in the Th1 cell proliferative response sustained by CD8(+) dendritic cells. J. Immunol., 169, 1182–8
Filippi, C., Hugues, S., Cazareth, J., Julia, V., Glaichenhaus, N. and Ugolini, S. (2003). CD4+ T cell polarization in mice is modulated by strain-specific major histocompatibility complex-independent differences within dendritic cells. J. Exp. Med., 198, 201–9
Fleeton, M. N., Contractor, N., Leon, F., Wetzel, J. D., Dermody, T. S. and Kelsall, B. L. (2004). Peyer's patch dendritic cells process viral antigen from apoptotic epithelial cells in the intestine of reovirus-infected mice. J. Exp. Med., 200, 235–45
Fujii, S., Shimizu, K., Smith, C., Bonifaz, L. and Steinman, R. M. (2003). Activation of natural killer T cells by alpha-galactosylceramide rapidly induces the full maturation of dendritic cells in vivo and thereby acts as an adjuvant for combined CD4 and CD8 T cell immunity to a coadministered protein. J. Exp. Med., 198, 267–79
Gilliet, M., Boonstra, A., Paturel, C., Antonenko, S., Xu, X. L., Trinchieri, G., O'Garra, A. and Liu, Y. J. (2002). The development of murine plasmacytoid dendritic cell precursors is differentially regulated by FLT3-ligand and granulocyte/macrophage colony-stimulating factor. J. Exp. Med., 195, 953–8
Hacker, C., Kirsch, R. D., Ju, X. S., Hieronymus, T., Gust, T. C., Kuhl, C., Jorgas, T., Kurz, S. M., Rose-John, S., Yokota, Y. and Zenke, M. (2003). Transcriptional profiling identifies Id2 function in dendritic cell development. Nat. Immunol., 4, 380–6
Henri, S., Vremec, D., Kamath, A., Waithman, J., Williams, S., Benoist, C., Burnham, K., Saeland, S., Handman, E. and Shortman, K. (2001). The dendritic cell populations of mouse lymph nodes. J. Immunol., 167, 741–8
Honda, K., Mizutani, T. and Taniguchi, T. (2004). Negative regulation of interferon-alpha/beta signaling by interferon regulatory factor 2 for homeostatic development of dendritic cells. Proc. Natl Acad. Sci. U S A, 101, 2416–21
Ichikawa, E., Hida, S., Omatsu, Y., Shimoyama, S., Takahara, K., Miyagawa, S., Inaba, K. and Taki, S. (2004). Defective development of splenic and epidermal CD4+ dendritic cells in mice deficient for interferon regulatory factor-2. Proc. Natl Acad. Sci. U S A, 101, 3909–14
Itano, A. A., McSorley, S. J., Reinhardt, R. L., Ehst, B. D., Ingulli, E., Rudensky, A. Y. and Jenkins, M. K. (2003). Distinct dendritic cell populations sequentially present antigen to CD4 T cells and stimulate different aspects of cell-mediated immunity. Immunity, 19, 47–57
Iwasaki, A. (2003). The importance of CD11b+ dendritic cells in CD4+ T cell activation in vivo: with help from interleukin 1. J. Exp. Med., 198, 185–90
Iwasaki, A. and Kelsall, B. L. (1999). Freshly isolated Peyer's patch, but not spleen, dendritic cells produce interleukin 10 and induce the differentiation of T helper type 2 cells. J. Exp. Med., 190, 229–39
Iwasaki, A. and Kelsall, B. L. (2000). Localization of distinct Peyer's patch dendritic cell subsets and their recruitment by chemokines macrophage inflammatory protein (MIP)-3alpha, MIP-3beta, and secondary lymphoid organ chemokine. J. Exp. Med., 191, 1381–94
Iwasaki, A. and Kelsall, B. L. (2001). Unique functions of CD11b+, CD8 alpha+, and double-negative Peyer's patch dendritic cells. J. Immunol., 166, 4884–90
Iwasaki, A. and Medzhitov, R. (2004). Toll-like receptor control of the adaptive immune responses. Nat. Immunol., 5, 987–95
Iyoda, T., Shimoyama, S., Liu, K., Omatsu, Y., Akiyama, Y., Maeda, Y., Takahara, K., Steinman, R. M. and Inaba, K. (2002). The CD8+ dendritic cell subset selectively endocytoses dying cells in culture and in vivo. J. Exp. Med., 195, 1289–302
Johansson, C. and Kelsall, B. L. (2005). Phenotype and function of intestinal dendritic cells. Semin. Immunol., 17, 284–94
Kabashima, K., Banks, T. A., Ansel, K. M., Lu, T. T., Ware, C. F. and Cyster, J. G. (2005). Intrinsic lymphotoxin-beta receptor requirement for homeostasis of lymphoid tissue dendritic cells. Immunity, 22, 439–50
Kamogawa-Schifter, Y., Ohkawa, J., Namiki, S., Arai, N., Arai, K. and Liu, Y. (2005). Ly49Q defines 2 pdendritic cell subsets in mice. Blood, 105, 2787–92
Karsunky, H., Merad, M., Mende, I., Manz, M. G., Engleman, E. G. and Weissman, I. L. (2005). Developmental origin of interferon-alpha-producing dendritic cells from hematopoietic precursors. Exp. Hematol., 33, 173–81
Kobayashi, T., Walsh, P. T., Walsh, M. C., Speirs, K. M., Chiffoleau, E., King, C. G., Hancock, W. W., Caamano, J. H., Hunter, C. A., Scott, P., Turka, L. A. and Choi, Y. (2003). TRAF6 is a critical factor for dendritic cell maturation and development. Immunity, 19, 353–63
Krug, A., Veeraswamy, R., Pekosz, A., Kanagawa, O., Unanue, E. R., Colonna, M. and Cella, M. (2003). Interferon-producing cells fail to induce proliferation of naive T cells but can promote expansion and T helper 1 differentiation of antigen-experienced unpolarized T cells. J. Exp. Med., 197, 899–906
Krug, A., French, A. R., Barchet, W., Fischer, J. A., Dzionek, A., Pingel, J. T., Orihuela, M. M., Akira, S., Yokoyama, W. M. and Colonna, M. (2004). Toll-like receptor9-dependent recognition of MCMV by IPC and dendritic cell generates coordinated cytokine responses that activate antiviral natural killer cell function. Immunity, 21, 107–19
Laouar, Y., Welte, T., Fu, X. Y. and Flavell, R. A. (2003). STAT3 is required for Flt3L-dependent dendritic cell differentiation. Immunity, 19, 903–12
Leenen, P. J., Radosevic, K., Voerman, J. S., Salomon, B., Rooijen, N., Klatzmann, D. and Ewijk, W. (1998). Heterogeneity of mouse spleen dendritic cells: in vivo phagocytic activity, expression of macrophage markers, and subpopulation turnover. J. Immunol., 160, 2166–73
Leon, B., Lopez-Bravo, M. and Ardavín, C. (2005). Monocyte-derived dendritic cells. Semin. Immunol., 17, 313–18
Liu, K., Iyoda, T., Saternus, M., Kimura, Y., Inaba, K. and Steinman, R. M. (2002). Immune tolerance after delivery of dying cells to dendritic cells in situ. J. Exp. Med., 196, 1091–7
Maldonado-Lopez, R., Maliszewski, C., Urbain, J. and Moser, M. (2001). Cytokines regulate the capacity of CD8alpha(+) and CD8alpha(−) dendritic cells to prime Th1/Th2 cells in vivo. J. Immunol., 167, 4345–50
Manz, M. G., Traver, D., Miyamoto, T., Weissman, I. L. and Akashi, K. (2001). Dendritic cell potentials of early lymphoid and myeloid progenitors. Blood, 97, 3333–41
Martin, P., Ruiz, S. R., del Hoyo, G. M., Anjuere, F., Vargas, H. H., Lopez-Bravo, M. and Ardavín, C. (2002). Dramatic increase in lymph node dendritic cell number during infection by the mouse mammary tumor virus occurs by a CD62L-dependent blood-borne dendritic cell recruitment. Blood, 99, 1282–8
Mayerova, D., Parke, E. A., Bursch, L. S., Odumade, O. A. and Hogquist, K. A. (2004). Langerhans cells activate naive self-antigen-specific CD8 T cells in the steady state. Immunity, 21, 391–400
McKenna, H. J., Stocking, K. L., Miller, R. E., Brasel, K., Smedt, T., Maraskovsky, E., Maliszewski, C. R., Lynch, D. H., Smith, J., Pulendran, B., Roux, E. R., Teepe, M., Lyman, S. D. and Peschon, J. J. (2000). Mice lacking flt3 ligand have deficient hematopoiesis affecting hematopoietic progenitor cells, dendritic cells, and natural killer cells. Blood, 95, 3489–97
Pooley, J. L., Heath, W. R. and Shortman, K. (2001). Cutting edge: intravenous soluble antigen is presented to CD4 T cells by CD8-dendritic cells, but cross-presented to CD8 T cells by CD8+ dendritic cells. J. Immunol., 166, 5327–30
Prakash, A., Smith, E., Lee, C. K. and Levy, D. E. (2005). Tissue-specific positive feedback requirements for production of type I interferon following virus infection. J. Biol. Chem., 280, 18651–7
Sousa, C. Reis e, Hieny, S., Scharton-Kersten, T., Jankovic, D., Charest, H., Germain, R. N. and Sher, A. (1997). In vivo microbial stimulation induces rapid CD40 ligand-independent production of interleukin 12 by dendritic cells and their redistribution to T cell areas. J. Exp. Med., 186, 1819–29
Rescigno, M., Urbano, M., Valzasina, B., Francolini, M., Rotta, G., Bonasio, R., Granucci, F., Kraehenbuhl, J. P. and Ricciardi-Castagnoli, P. (2001). Dendritic cells express tight junction proteins and penetrate gut epithelial monolayers to sample bacteria. Nat. Immunol., 2, 361–7
Ritter, U., Meissner, A., Scheidig, C. and Korner, H. (2004). CD8 alpha- and Langerin-negative dendritic cells, but not Langerhans cells, act as principal antigen-presenting cells in leishmaniasis. Eur. J. Immunol., 34, 1542–50
Sato, A., Hashiguchi, M., Toda, E., Iwasaki, A., Hachimura, S. and Kaminogawa, S. (2003). CD11b+ Peyer's patch dendritic cells secrete interleukin-6 and induce IgA secretion from naive B cells. J. Immunol., 171, 3684–90
Scheinecker, C., McHugh, R., Shevach, E. M. and Germain, R. N. (2002). Constitutive presentation of a natural tissue autoantigen exclusively by dendritic cells in the draining lymph node. J. Exp. Med., 196, 1079–90
Schiavoni, G., Mattei, F., Sestili, P., Borghi, P., Venditti, M., Morse, H. C., 3rd, , Belardelli, F. and Gabriele, L. (2002). ICSBP is essential for the development of mouse type I interferon-producing cells and for the generation and activation of CD8alpha(+) dendritic cells. J. Exp. Med., 196, 1415–25
Schiavoni, G., Mattei, F., Borghi, P., Sestili, P., Venditti, M., Morse, H. C., 3rd, , Belardelli, F. and Gabriele, L. (2004). ICSBP is critically involved in the normal development and trafficking of Langerhans cells and dermal dendritic cells. Blood, 103, 2221–8
Schlecht, G., Garcia, S., Escriou, N., Freitas, A. A., Leclerc, C. and Dadaglio, G. (2004). Murine plasmacytoid dendritic cells induce effector/memory CD8+ T-cell responses in vivo after viral stimulation. Blood, 104, 1808–15
Schulz, O. and Sousa, C. Reis e (2002). Cross-presentation of cell-associated antigens by CD8alpha+ dendritic cells is attributable to their ability to internalize dead cells. Immunology, 107, 183–9
Shigematsu, H., Reizis, B., Iwasaki, H., Mizuno, S., Hu, D., Traver, D., Leder, P., Sakaguchi, N. and Akashi, K. (2004). Plasmacytoid dendritic cells activate lymphoid-specific genetic programs irrespective of their cellular origin. Immunity, 21, 43–53
Shortman, K. and Liu, Y. J. (2002). Mouse and human dendritic cell subtypes. Nat. Rev. Immunol., 2, 151–61
Steinman, R. M. and Nussenzweig, M. C. (2002). Avoiding horror autotoxicus: the importance of dendritic cells in peripheral T cell tolerance. Proc. Natl Acad. Sci. U S A, 99, 351–8
Suzuki, S., Honma, K., Matsuyama, T., Suzuki, K., Toriyama, K., Akitoyo, I., Yamamoto, K., Suematsu, T., Nakamura, M., Yui, K. and Kumatori, A. (2004). Critical roles of interferon regulatory factor 4 in CD11bhighCD8alpha− dendritic cell development. Proc. Natl Acad. Sci. U S A, 101, 8981–6
Tamura, T., Tailor, P., Yamaoka, K., Kong, H. J., Tsujimura, H., O'Shea, J. J., Singh, H. and Ozato, K. (2005). interferon regulatory factor-4 and -8 govern dendritic cell subset development and their functional diversity. J. Immunol., 174, 2573–81
Thery, C., Duban, L., Segura, E., Veron, P., Lantz, O. and Amigorena, S. (2002). Indirect activation of naive CD4+ T cells by dendritic cell-derived exosomes. Nat. Immunol., 3, 1156–62
Traver, D., Akashi, K., Manz, M., Merad, M., Miyamoto, T., Engleman, E. G. and Weissman, I. L. (2000). Development of CD8alpha-positive dendritic cells from a common myeloid progenitor. Science, 290, 2152–4
Tsujimura, H., Tamura, T. and Ozato, K. (2003). Cutting edge: interferon consensus sequence binding protein/interferon regulatory factor 8 drives the development of type I interferon-producing plasmacytoid dendritic cells. J. Immunol., 170, 1131–5
Turley, S., Poirot, L., Hattori, M., Benoist, C. and Mathis, D. (2003). Physiological beta cell death triggers priming of self-reactive T cells by dendritic cells in a type-1 diabetes model. J. Exp. Med., 198, 1527–37
Valladeau, J. and Saeland, S. (2005). Cutaneous dendritic cells. Semin. Immunol., 17, 273–83
Villadangos, J. A. and Heath, W. R. (2005). Life cycle, migration and antigen presenting functions of spleen and lymph node dendritic cells: Limitations of the Langerhans cells paradigm. Semin. Immunol., 17, 262–72
Wu, L., Nichogiannopoulou, A., Shortman, K. and Georgopoulos, K. (1997). Cell-autonomous defects in dendritic cell populations of Ikaros mutant mice point to a developmental relationship with the lymphoid lineage. Immunity, 7, 483–92
Wu, L., D'Amico, A., Winkel, K. D., Suter, M., Lo, D. and Shortman, K. (1998). RelB is essential for the development of myeloid-related CD8alpha− dendritic cells but not of lymphoid-related CD8alpha+ dendritic cells. Immunity, 9, 839–47
Wu, L., D'Amico, A., Hochrein, H., O'Keeffe, M., Shortman, K. and Lucas, K. (2001). Development of thymic and splenic dendritic cell populations from different hemopoietic precursors. Blood, 98, 3376–82
Zhang, Y., Zhang, Y. Y., Ogata, M., Chen, P., Harada, A., Hashimoto, S. and Matsushima, K. (1999). Transforming growth factor-beta1 polarizes murine hematopoietic progenitor cells to generate Langerhans cell-like dendritic cells through a monocyte/macrophage differentiation pathway. Blood, 93, 1208–20