Invited review article| Volume 45, ISSUE 2, P77-86, February 2007

Download started.


Dendritic cell immunoreceptors: C-type lectin receptors for pattern-recognition and signaling on antigen-presenting cells


      C-type lectin receptors are equipped on phagocytes for antigen capturing. Some of them seem to have a major role in cellular activation, rather than antigen internalization. The dendritic cell (DC) immunoreceptor (DCIR) and DC-associated C-type lectin (dectin)-1 have been identified as prototypic DC-associated C-type lectin receptors, characterized by their signaling mechanisms through distinct intracellular motifs; the former contains the immunoreceptor tyrosine-based inhibitory motif (ITIM), to act as an inhibitory receptor, whereas the latter works as an activating receptor via its immunoreceptor tyrosine-based activation motif (ITAM). Genes of both receptors are localized very close to the natural killer (NK) gene complex (NKC), in which genes of lectin-type activating and inhibitory NK cell receptors are clustered. Recently, the gene of the DC immunoactivating receptor (DCAR) has been identified next to the DCIR gene, and this acts as a putative activating pair of DCIR through association with an ITAM-bearing Fc receptor (FcR) γ chain. On the other hand, the gene of an ITIM-bearing myeloid inhibitory C-type lectin-like receptor (MICL) has been found close to the dectin-1 gene. The genes of other homologous DC-associated C-type lectin receptors, dectin-2 and blood DC antigen (BDCA)-2, form a cluster with those of DCIR and DCAR, while the dectin-1 gene cluster contains lectin-like oxidized low-density lipoprotein receptor (LOX)-1, C-type lectin-like receptor (CLEC)-1 and 2, as well as MICL. Although no ligand of DCIR has yet been identified, dectin-1 recognizes fungal β-glucan and its critical role in the biological effects of β-glucan has been vigorously investigated. In this review, the characteristic features of these DCIR and dectin-1 family lectins, including the signaling mechanisms, ligand recognition and regulation of cellular functions, are summarized and the term “DC immunoreceptors” is applied to a distinct set of signaling pattern-recognition receptors described here.


      APC (antigen-presenting cell), BCR (B cell receptor), CHS (contact hypersensitivity), CLEC (C-type lectin domain family), CRD (carbohydrate recognition domain), CTLD (C-type lectin-like domain), DC (dendritic cell), FcR (Fc receptor), IFN (interferon), Ig (immunoglobulin), IL (interleukin), ITAM (immunoreceptor tyrosine-based activation motif), ITIM (immunoreceptor tyrosine-based inhibitory motif), LC (Langerhans cell), LPS (lipopolysaccharide), mAb (monoclonal antibody), MAPK (mitogen-activated protein kinase), MHC (major histocompatibility complex), moDC (monocyte-derived DC), NF (nuclear factor), NK (natural killer), NKC (NK gene complex), OxLDL (oxidized low-density lipoprotein), PDC (plasmacytoid DC), PRR (pattern-recognition receptor), PTK (protein tyrosine kinase), SH2 (Src homology 2), SHP (SH2 domain-containing protein tyrosine phosphatase), TCR (T cell receptor), TLR (Toll-like receptor), UV (ultraviolet)


      To read this article in full you will need to make a payment

      Purchase one-time access:

      Academic & Personal: 24 hour online accessCorporate R&D Professionals: 24 hour online access
      One-time access price info
      • For academic or personal research use, select 'Academic and Personal'
      • For corporate R&D use, select 'Corporate R&D Professionals'


      Subscribe to Journal of Dermatological Science
      Already a print subscriber? Claim online access
      Already an online subscriber? Sign in
      Institutional Access: Sign in to ScienceDirect


        • Takeda K.
        • Akira S.
        Microbial recognition by Toll-like receptors.
        J Dermatol Sci. 2004; 34: 73-82
        • Akira S.
        • Uematsu S.
        • Takeuchi O.
        Pathogen recognition and innate immunity.
        Cell. 2006; 124: 783-801
        • Kambe N.
        • Nishikomori R.
        • Kanazawa N.
        The cytosolic pattern-recognition receptor Nod2 and inflammatory granulomatous disorders.
        J Dermatol Sci. 2005; 39: 71-80
        • Brown G.D.
        Dectin-1: a signalling non-TLR pattern-recognition receptor.
        Nat Rev Immunol. 2006; 6: 33-43
        • Weis W.I.
        • Taylor M.E.
        • Drickamer K.
        The C-type lectin superfamily in the immune system.
        Immunol Rev. 1998; 163: 19-34
        • McGreal E.P.
        • Miller J.L.
        • Gordon S.
        Ligand recognition by antigen-presenting cell C-type lectin receptors.
        Curr Opin Immunol. 2005; 17: 18-24
        • East L.
        • Isacke C.M.
        The mannose receptor family.
        Biochem Biophys Acta. 2002; 1572: 364-386
        • Geijtenbeek T.B.
        • van Vliet S.J.
        • Engering A.
        • ’t Hart B.A.
        • van Kooyk Y.
        Self- and nonself-recognition by C-type lectins on dendritic cells.
        Annu Rev Immunol. 2004; 22: 33-54
        • van Kooyk Y.
        • Geijtenbeek T.B.
        DC-SIGN: escape mechanism for pathogens.
        Nat Rev Immunol. 2003; 3: 697-709
        • van Vliet S.J.
        • van Liempt E.
        • Saeland E.
        • et al.
        Carbohydrate profiling reveals a distinctive role for the C-type lectin MGL in the recognition of helminth parasites and tumor antigens by dendritic cells.
        Int Immunol. 2005; 17: 661-669
        • Gergely J.
        • Pecht I.
        • Sarmay G.
        Immunoreceptor tyrosine-based inhibition motif-bearing receptors regulate the immunoreceptor tyrosine-based activation motif-induced activation of immune competent cells.
        Immunol Lett. 1999; 68: 3-15
        • Bakker A.B.
        • Hoek R.M.
        • Cerwenka A.
        • Blom B.
        • Lucian L.
        • McNeil T.
        • et al.
        DAP12-deficient mice fail to develop autoimmunity due to impaired antigen priming.
        Immunity. 2000; 13: 345-353
        • Hamano Y.
        • Arase H.
        • Saisho H.
        • Saito T.
        Immune complex and Fc receptor-mediated augmentation of antigen presentation for in vivo Th cell responses.
        J Immunol. 2000; 164: 6113-6119
        • Veillette A.
        • Latour S.
        • Davidson D.
        Negative regulation of immunoreceptor signaling.
        Annu Rev Immunol. 2002; 20: 669-707
        • Yokoyama W.M.
        • Plougastel B.F.
        Immune functions encoded by the natural killer gene complex.
        Nat Rev Immunol. 2003; 3: 304-316
        • Martin A.M.
        • Kulski J.K.
        • Witt C.
        • Pontarotti P.
        • Christiansen F.T.
        Leukocyte Ig-like receptor complex (LRC) in mice and men.
        Trends Immunol. 2002; 23: 81-88
        • Kanazawa N.
        • Tashiro K.
        • Miyachi Y.
        Signaling and immune regulatory role of the dendritic cell immunoreceptor (DCIR) family lectins: DCIR, DCAR, dectin-2 and BDCA-2.
        Immunobiology. 2004; 209: 179-190
        • Kanazawa N.
        • Tashiro K.
        • Inaba K.
        • Miyachi Y.
        Dendritic cell immunoactivating receptor, a novel C-type lectin immunoreceptor, acts as an activating receptor through association with Fc receptor γ chain.
        J Biol Chem. 2003; 278: 32645-32652
        • Ariizumi K.
        • Shen G.L.
        • Shikano S.
        • et al.
        Identification of a novel, dendritic cell-associated molecule, dectin-1, by subtractive cDNA cloning.
        J Biol Chem. 2000; 275: 20157-20167
        • Bates E.E.
        • Fournier N.
        • Garcia E.
        • et al.
        APCs express DCIR, a novel C-type lectin surface receptor containing an immunoreceptor tyrosine-based inhibitory motif.
        J Immunol. 1999; 163: 1973-1983
        • Kanazawa N.
        • Okazaki T.
        • Nishimura H.
        • Tashiro K.
        • Inaba K.
        • Miyachi Y.
        DCIR acts as an inhibitory receptor depending on its immunoreceptor tyrosine-based inhibitory motif.
        J Invest Dermatol. 2002; 118: 261-266
        • Huang X.
        • Yuan Z.
        • Chen G.
        • Zhang M.
        • Zhang W.
        • Yu Y.
        • et al.
        Cloning and characterization of a novel ITIM containing lectin-like immunoreceptor LLIR and its two transmembrane region deletion variants.
        Biochem Biophys Res Commun. 2001; 281: 131-140
        • Richard M.
        • Thibault N.
        • Veilleux P.
        • Gareau-Page G.
        • Beaulieu A.D.
        Granulocyte macrophage-colony stimulating factor reduces the affinity of SHP-2 for the ITIM of CLECSF6 in neutrophils: a new mechanism of action for SHP-2.
        Mol Immunol. 2006; 43: 1716-1721
        • Drickamer K.
        Evolution of Ca2+-dependent animal lectins.
        Prog Nucl Acid Res. 1993; 45: 207-232
        • Ariizumi K.
        • Shen G.L.
        • Shikano S.
        • Ritter III, R.
        • Zukas P.
        • Edelbaum D.
        • et al.
        Cloning of a second dendritic cell-associated C-type lectin (dectin-2) and its alternatively spliced isoforms.
        J Biol Chem. 2000; 275: 11957-11963
        • Fernandes M.J.
        • Finnegan A.A.
        • Siracusa L.D.
        • Brenner C.
        • Iscove N.N.
        • Calabretta B.
        Characterization of a novel receptor that maps near the natural killer gene complex: demonstration of carbohydrate binding and expression in hematopoietic cells.
        Cancer Res. 1999; 59: 2709-2717
        • Kanazawa N.
        • Tashiro K.
        • Inaba K.
        • Lutz M.B.
        • Miyachi Y.
        Molecular cloning of human dectin-2.
        J Invest Dermatol. 2004; 122: 1522-1524
        • Gavino A.C.
        • Chung J.S.
        • Sato K.
        • Ariizumi K.
        • Cruz Jr., P.D.
        Identification and expression profiling of a human C-type lectin, structurally homologous to mouse dectin-2.
        Exp Dermatol. 2005; 14: 281-288
        • McGreal E.P.
        • Rosas M.
        • Brown G.D.
        • Zamze S.
        • Wong S.Y.
        • Gordon S.
        • et al.
        The carbohydrate-recognition domain of dectin-2 is a C-type lectin with specificity for high mannose.
        Glycobiology. 2006; 16: 422-430
        • Aragane Y.
        • Maeda A.
        • Schwarz A.
        • Tezuka T.
        • Ariizumi K.
        • Schwarz T.
        Involvement of dectin-2 in ultraviolet radiation-induced tolerance.
        J Immunol. 2003; 171: 3801-3807
        • Bonkobara M.
        • Yagihara H.
        • Yudate T.
        • Chung J.S.
        • Washizu T.
        • Ariizumi K.
        • et al.
        Ultraviolet-B radiation upregulates expression of dectin-2 on epidermal Langerhans cells by activating the gene promoter.
        Photochem Photobiol. 2005; 81: 944-948
        • Dzionek A.
        • Sohma Y.
        • Nagafune J.
        • et al.
        BDCA-2, a novel plasmacytoid dendritic cell-specific type II C-type lectin, mediates antigen capture and is a potent inhibitor of interferon α/β induction.
        J Exp Med. 2001; 194: 1823-1834
        • Arce I.
        • Roda-Navarro P.
        • Montoya M.C.
        • Hernanz-Falcon P.
        • Puig-Kroger A.
        • Fernandez-Ruiz E.
        Molecular and genomic characterization of human DLEC, a novel member of the C-type lectin receptor gene family preferentially expressed on monocyte-derived dendritic cells.
        Eur J Immunol. 2001; 31: 2733-2740
        • Dzionek A.
        • Inagaki Y.
        • Okawa K.
        • et al.
        Plasmacytoid dendritic cells: from specific surface markers to specific cellular functions.
        Hum Immunol. 2002; 63: 1133-1148
        • Nestle F.O.
        • Conrad C.
        • Tun-Kyi A.
        • Homey B.
        • Gombert M.
        • Boyman O.
        • et al.
        Plasmacytoid predendritic cells initiate psoriasis through interferon-alpha production.
        J Exp Med. 2005; 202: 135-143
        • Jaehn P.
        • Schmitz J.
        • Dzionek A.
        Targeting of antigen to plasmacytoid dendritic cells (PDCS) via the type II C-type lectin BDCA-2.
        in: Proceedings of the eighth international symposium on dendritic cells, meeting abstract. 2004
        • Arce I.
        • Martinez-Munoz L.
        • Roda-Navarro P.
        • Fernandez-Ruiz E.
        The human C-type lectin CLECSF8 is a novel monocyte/macrophage endocytic receptor.
        Eur J Immunol. 2004; 34: 210-220
        • Heinsbroek S.E.
        • Brown G.D.
        • Gordon S.
        Dectin-1 escape by fungal dimorphism.
        Trends Immunol. 2005; 26: 352-354
        • Yoshitomi H.
        • Sakaguchi N.
        • Kobayashi K.
        • et al.
        A role for fungal β-glucans and their receptor dectin-1 in the induction of autoimmune arthritis in genetically susceptible mice.
        J Exp Med. 2005; 201: 949-960
        • Keystone E.C.
        • Schorlemmer H.U.
        • Pope C.
        • et al.
        Zymosan-induced arthritis: a model of chronic proliferative arthritis following activation of the alternative pathway of complement.
        Arthritis Rheum. 1977; 20: 1396-1401
        • Chen M.
        • Masaki T.
        • Sawamura T.
        LOX-1, the receptor for oxidized low-density lipoprotein identified from endothelial cells: implications in endothelial dysfunction and atherosclerosis.
        Pharmacol Ther. 2002; 95: 89-100
        • Delneste Y.
        • Magistrelli G.
        • Gauchat J.
        • et al.
        Involvement of LOX-1 in dendritic cell-mediated antigen cross-presentation.
        Immunity. 2002; 17: 353-362
        • Jeannin P.
        • Bottazzi B.
        • Sironi M.
        • et al.
        Complexity and complementarity of outer membrane protein A recognition by cellular and humoral innate immunity receptors.
        Immunity. 2005; 22: 551-560
        • Colonna M.
        • Samaridis J.
        • Angman L.
        Molecular characterization of two novel C-type lectin-like receptors, one of which is selectively expressed in human dendritic cells.
        Eur J Immunol. 2000; 30: 697-704
        • Suzuki-Inoue K.
        • Fuller G.L.
        • Garcia A.
        • et al.
        A novel Syk-dependent mechanism of platelet activation by the C-type lectin receptor CLEC-2.
        Blood. 2006; 107: 542-549
        • Marshall A.S.
        • Willment J.A.
        • Lin H.H.
        • Williams D.L.
        • Gordon S.
        • Brown G.D.
        The identification and characterization of a novel human myeloid inhibitory C-type lectin-like receptor, MICL, which is predominantly expressed on granulocytes and monocytes.
        J Biol Chem. 2004; 279: 14792-14802
        • Chen C.H.
        • Floyd H.
        • Olson N.E.
        • Magaletti D.
        • Li C.
        • Draves K.
        • et al.
        Dendritic-cell-associated C-type lectin 2 (DCAL-2) alters dendritic-cell maturation and cytokine production.
        Blood. 2006; 107: 1459-1467
        • Ohl L.
        • Mohaupt M.
        • Czeloth N.
        • et al.
        CCR7 governs skin dendritic cell migration under inflammatory and steady-state conditions.
        Immunity. 2004; 21: 279-288
        • Hamerman J.A.
        • Tchao N.K.
        • Lowell C.A.
        • Lanier L.L.
        Enhanced Toll-like receptor responses in the absence of signaling adaptor DAP12.
        Nat Immunol. 2005; 6: 579-586
        • Flornes L.M.
        • Bryceson Y.T.
        • Spurkland A.
        • Lorentzen J.C.
        • Dissen E.
        • Fossum S.
        Identification of lectin-like receptors expressed by antigen presenting cells and neutrophils and their mapping to a novel gene complex.
        Immunogenetics. 2004; 56: 506-517


      Nobuo Kanazawa graduated and received the MD degree from Kyoto University Faculty of Medicine in 1994 and was trained at the Department of Dermatology. From 1996, he studied molecular biology and immunology at the Department of Molecular Biology of Kyoto University Graduate School of Medicine (Prof. T. Honjo) and obtained the PhD degree in 2000. He was a staff of the Department of Dermatology, Kyoto University Graduate School of Medicine from 2001 to 2005. Since 2003, he spent almost 2 years as a postdoctoral research fellow at the Department of Dermatology, University of Erlangen, Germany (Prof. G. Schuler). In 2006, he moved to Wakayama Medical University, where he is an assistant professor in the Department of Dermatology.