Identification of a Novel, Dendritic Cell-associated Molecule, Dectin-1, by Subtractive cDNA Cloning

Ariizumi, Kiyoshi; Shen, Gang; Shikano, Sojin; Xu, Shan; Ritter, Robert; Kumamoto, Tadashi; Edelbaum, Dale; Morita, Akimichi; Bergstresser, Paul R.; Takashima, Akira

doi:10.1074/jbc.m909512199

Cited by 424 publications

(352 citation statements)

References 82 publications

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“…Our analysis of MICL, in both transduced cell lines [14] and primary cells, suggests that this molecule is highly N-glycosylated compared to its most closely related paralogs, lectin-like receptor for oxidized LDL [22], Dectin-1 [9,23], and CLEC-2 [13]. Intriguingly, the level of MICL N-glycosylation varied significantly in different leukocyte populations, which may have functional consequences for ligand binding, as shown for other receptors [24,25].…”

Section: Discussionmentioning

confidence: 65%

“…Others and we have demonstrated that C-type lectinlike receptors are not restricted to NK cells, but are expressed by many other cell types including myeloid cells [8][9][10]. This introduces the novel concept that the myeloid paralogs of NK cell receptors might govern myeloid cell activation/inhibition in the same manner as those on NK cells.…”

Section: Introductionmentioning

confidence: 88%

“…The study of these activationand inhibitory NK cell receptorshas generated a number of interesting hypotheses, including immune privilege [1], the recognition of 'missing self', 'non-self' and 'induced self' [2][3][4][5], as well elucidating the underlying mechanisms of some of the immune responses to viruses [6] and malignancy [7]. Others and we have demonstrated that C-type lectinlike receptors are not restricted to NK cells, but are expressed by many other cell types including myeloid cells [8][9][10]. This introduces the novel concept that the myeloid paralogs of NK cell receptors might govern myeloid cell activation/inhibition in the same manner as those on NK cells.…”

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confidence: 96%

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Human MICL (CLEC12A) is differentially glycosylated and is down‐regulated following cellular activation

Willment¹,

Pyż²,

Dennehy³

et al. 2006

Eur J Immunol

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C-type lectins are the most diverse and prevalent lectin family in immunity. Particular interest has recently been attracted by the C-type lectin-like receptors on NK cells, which appear to regulate the activation/inhibitory balance of these cells, controlling cytotoxicity and cytokine production. We previously identified a human C-type lectin-like receptor, closely related to both the beta-glucan receptor and the lectin-like receptor for oxidized-LDL, named MICL (myeloid inhibitory C-type lectin-like receptor), which we had shown using chimeric analysis to function as an inhibitory receptor. Using a novel MICL-specific monoclonal antibody, we show here that human MICL is expressed primarily on myeloid cells, including granulocytes, monocytes, macrophages, and dendritic cells. Although MICL was highly N-glycosylated in primary cells, the level of glycosylation was found to vary between cell types. MICL surface expression was down-regulated during inflammatory/activation conditions in vitro, as well as during an in vivo model of acute inflammation, which we characterize here. This suggests that human MICL may be involved in the control of myeloid cell activation during inflammation. IntroductionIn order to execute their immune (and non-immune) functions, leukocytes must interact with a broad range of endogenous and exogenous ligands and must be able to respond to these interactions appropriately. This requires a wide and flexible, yet specific and regulated, repertoire of cell surface molecules. One large family of such molecules, which are particularly important to immunity, are the C-type lectin and lectin-like receptors. C-type lectin-like receptors were first identified as dimeric molecules on NK cells. On these cells, much attention has been drawn toward their ability to regulate the balance between cellular activation and inhibition, such as cytotoxicity and cytokine production. This is achieved through signalling via intracellular ITIM present in the cytoplasmic tails of these receptors or via ITAM, of which the majority are located in the cytoplasmic tails of associated molecules, such as DAP12. The study of these activationand inhibitory NK cell receptorshas generated a number of interesting hypotheses, including immune privilege [1], the recognition of 'missing self', 'non-self' and 'induced self' [2][3][4][5], as well elucidating the underlying mechanisms of some of the immune responses to viruses [6] and malignancy [7]. Others and we have demonstrated that C-type lectinlike receptors are not restricted to NK cells, but are expressed by many other cell types including myeloid cells [8][9][10]. This introduces the novel concept that the myeloid paralogs of NK cell receptors might govern myeloid cell activation/inhibition in the same manner as those on NK cells. The genes of most C-type lectin-like molecules are located within the 'natural killer complex' (NKC), but many of those expressed by myeloid and other cells are found in a distinct cluster of genes within the NKC [10]. This cluster includes Decti...

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Section: Discussionmentioning

confidence: 65%

Section: Introductionmentioning

confidence: 88%

mentioning

confidence: 96%

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Human MICL (CLEC12A) is differentially glycosylated and is down‐regulated following cellular activation

Willment¹,

Pyż²,

Dennehy³

et al. 2006

Eur J Immunol

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“…other myeloid cells that lacks CRDs but acts as a major receptor for b-glucans, and thus recognizes and can endocytose a number of fungal species, including yeast and Aspergillus (Ariizumi et al, 2000;Brown, 2006). Unlike other CLRs, Dectin-1 has an activating ITAM motif in its cytoplasmic tail, and cross-linking this receptor leads to APC activation and pro inflammatory mediator production (Gantner et al, 2003;Brown, 2006), as well as synergistic interaction with other innate signaling molecules such as TLR2 (Gantner et al, 2003).…”

Section: Antibody-targeted Vaccines T Keler Et Almentioning

confidence: 99%

Antibody-targeted vaccines

Keler

Ramakrishna

et al. 2007

Oncogene

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“…Dectin-1 [6] and human (h) DC-SIGN (CD209) [7] are the most extensively studied members of this family. Dectin-1 is a major receptor for b-glucan [8], a component of the cell wall of Candida albicans, Pneumocystis carinii and Aspergillus fumigatus [8][9][10][11][12].…”

Section: Introductionmentioning

confidence: 99%

C‐type lectin SIGNR1 enhances cellular oxidative burst response against C. albicans in cooperation with Dectin‐1

et al. 2011

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We investigated the role of SIGNR1 in the recognition of Candida albicans and the subsequent cellular oxidative burst response. Soluble SIGNR1 (sSIGNR1) tetramer bound equally to zymosan and both heat-killed (HK) and live C. albicans in an EDTA-sensitive manner, whereas sDectin-1 tetramer predominantly bound to zymosan and HK-microbes in an EDTA-independent manner. In cellular response, enhanced oxidative burst was observed in RAW264.7 cells expressing SIGNR1 (RAW-SIGNR1) compared with RAW-control cells upon stimulation with HK-C. albicans and zymosan. This response was independent of TLR2 and the cytosolic portion of SIGNR1 but dependent on the recognition by SIGNR1 via carbohydrate recognition domain. Antagonistic laminarin and anti-Dectin-1 mAb cooperatively reduced the response with mannan and anti-SIGNR1 mAb, respectively, although they had no effect by themselves. Moreover, oxidative response and bactericidal activity largely relied on Syk-mediated signaling. RAW-SIGNR1 cells not only captured microbes more efficiently but also showed higher responses than RAW-control cells. Similar enhanced responses were observed in SIGNR-1-expressing resident peritoneal M/. Interestingly, Dectin-1 was recruited to the phagosomal membrane upon the stimulation and physically associated with SIGNR1. These results suggest that SIGNR1 plays a significant role in inducing oxidative response to C. albicans by Syk-dependent signaling, possibly through Dectin-1.Key words: C. albicans . Dectin-1 . Macrophages . SIGNR1 . TLR2 IntroductionInnate immunity is a crucial host defense system that eliminates pathogens as they initiate an infection and leads to the subsequent initiation of the adaptive immune response [1]. The system consists of germline-encoded genes, i.e. toll-like receptors (TLRs) [2] [8][9][10][11][12]. Microbe-mediated stimulation of Dectin-1 results in cellular oxidative burst and cytokine production through its ITAM and the Syk kinase pathway [13,14]. In addition, Dectin-1 has been shown to function collaboratively with TLR2 to stimulate cytokine production [15] and Th17/Treg induction [16].hDC-SIGN recognizes mannose and fucose moieties in the surface of a variety of microbes and viruses, such as Mycobacteria, Leishmania, Salmonella, Candida species, HIV, HCV, dengue virus, CMV, Ebola virus and Sindbis virus (refer to [17]). However, pathogens, i.e. HIV and HCV, have also found ways to subvert and use hDC-SIGN to their advantage [18,19]. Mycobacterium tuberculosis and HIV also target hDC-SIGN in order to upregulate DC production of the immunosuppressive cytokine IL-10 through Raf-1 kinase activation, which induces acetylation of the NF-kB p65 subunit in the presence of co-signaling from TLR4 [20].Mice have eight hDC-SIGN homologues [21,22]. One of these homologues, SIGNR1, has been shown to be expressed on particular Mf subsets in the marginal zone of the spleen, medulla of the lymph nodes and the peritoneal cavity [23][24][25] and to possess mannosebinding activities like hDC-SIGN. SIGNR1 recognizes not only vari...

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Identification of a Novel, Dendritic Cell-associated Molecule, Dectin-1, by Subtractive cDNA Cloning

Cited by 424 publications

References 82 publications

Human MICL (CLEC12A) is differentially glycosylated and is down‐regulated following cellular activation

Human MICL (CLEC12A) is differentially glycosylated and is down‐regulated following cellular activation

Antibody-targeted vaccines

C‐type lectin SIGNR1 enhances cellular oxidative burst response against C. albicans in cooperation with Dectin‐1

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