The DC-SIGN–related lectin LSECtin mediates antigen capture and pathogen binding by human myeloid cells

Domínguez-Soto, Ángeles; Aragoneses-Fenoll, Laura; Martín‐Gayo, Enrique; Martínez‐Prats, Lorena; Colmenares, Marı́a; Naranjo-Gómez, Mar; Borràs, Francesc E.; Muñoz, Pilar; Zubiaur, Mercedes; Toribio, Marı́a L.; Delgado, Rafaël; Corbí, Ángel L.

doi:10.1182/blood-2006-09-048058

Cited by 86 publications

(100 citation statements)

References 37 publications

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“…Monocytes were purified from peripheral blood mononuclear cells via magnetic cell sorting using CD14 microbeads (Miltenyi Biotech, Bergisch Gladbach, Germany), and monocyte-derived dendritic cells (MDDCs) were generated as described. 5,6 The K562 (chronic myelogenous leukemia) and THP-1 (monocytic leukemia) cell lines were cultured in Roswell Park Memorial Institute 1640 medium supplemented with 10% fetal bovine serum, 25 mM 4-(2-hydroxyethyl)-1-piperazine ethanesulfonic acid, and 2 mM glutamine (complete medium), at 37°C in a humidified atmosphere with 5% CO 2 . MUTZ-3 cells [23][24][25] were maintained in complete medium supplemented with granulocyte-macrophage colony-stimulating factor (10 ng/mL) and their dendritic differentiation was induced in the presence of 1,000 U/mL interleukin-4 (IL-4) for 5 days.…”

Section: Methodsmentioning

confidence: 99%

“…EnVisionTM G/2 Doublestain System (Dako) was used for the simultaneous detection of CD68 and LSECtin, following the manufacturer's recommendations with a mouse monoclonal antibody against CD68 (PG-M1; Dako) and the LSECtin-specific polyclonal antisera ADS1 (against the stalk domain) and ADS4 (against the whole extracellular region). 5,6 Blockade of endogenous peroxidase and alkaline phosphatase activities was accomplished with 0.5% H 2 O 2 and enzymatic inhibitors (Dako). After addition of the anti-CD68 antibody (1/100 dilution) for 30 minutes, tissue was incubated with dextran polymerconjugated horseradish peroxidase-labeled antisera against murine and rabbit immunoglobulins, and CD68-specific staining detected with 3,3'-diaminobenzidine.…”

Section: Methodsmentioning

confidence: 99%

“…16,17 Although reported to be exclusively expressed on liver and lymph node sinusoidal endothelial cells, 4 LSECtin has been later found to be expressed in ex vivo isolated human peripheral blood and thymic DCs, as well as in DCs and alternatively activated macrophages generated in vitro. 5 The carbohydrate specificity of LSECtin has been recently determined, 18 and a scavenging function has been proposed because of its ability to recognize glycoproteins with truncated complex and hybrid N-linked glycans terminating in GlcNAcMan.…”

mentioning

confidence: 99%

“…DC-SIGN, L-SIGN, and LSECtin function as endocytic receptors and mediate binding and internalization of clinically relevant viral, bacterial, and fungal pathogens. 5,6 CD23 is expressed on myeloid cells and activated B lymphocytes, where it functions as a low affinity receptor for immunoglobulin E and plays a role in limiting the extent of immunoglobulin E-mediated pathologies. 7,8 DC-SIGN is expressed on myeloid dendritic cells (DCs), 1,9 alternatively activated in vitro macrophages, 10 interstitial DCs, 11 a subset of CD14ϩ peripheral blood DCs, 12 and macrophages from various tissues, [13][14][15] whereas L-SIGN is exclusively expressed on endothelial cells of the liver, lymph nodes, and placenta.…”

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confidence: 99%

“…21 In fact, Kupffer cells mediate the removal of particulate material from the portal circulation. 22 The presence of LSECtin in myeloid cell subsets 5 prompted us to clarify its cell distribution in liver cells. We report that LSECtin is expressed in human Kupffer cells, where its expression correlates with the presence of the myeloid-restricted CD68 molecule.…”

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confidence: 99%

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The pathogen receptor liver and lymph node sinusoidal endotelial cell C-type lectin is expressed in human Kupffer cells and regulated by PU.1

et al. 2008

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Section: Methodsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

mentioning

confidence: 99%

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confidence: 99%

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The pathogen receptor liver and lymph node sinusoidal endotelial cell C-type lectin is expressed in human Kupffer cells and regulated by PU.1

et al. 2008

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Molecular Recognition in C‐Type Lectins: The Cases of DC‐SIGN, Langerin, MGL, and L‐Sectin

et al. 2020

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Carbohydrates play a pivotal role in intercellular communication processes. In particular, glycan antigens are key for sustaining homeostasis, helping leukocytes to distinguish damaged tissues and invading pathogens from healthy tissues. From a structural perspective, this cross-talk is fairly complex, and multiple membrane proteins guide these recognition processes, including lectins and Toll-like receptors. Since the beginning of this century, lectins have become potential targets for therapeutics for controlling and/or avoiding the progression of pathologies derived from an incorrect immune outcome, including infectious processes, cancer, or autoimmune diseases. Therefore, a detailed knowledge of these receptors is mandatory for the development of specific treatments. In this review, we summarize the current knowledge about four key C-type lectins whose importance has been steadily growing in recent years, focusing in particular on how glycan recognition takes place at the molecular level, but also looking at recent progresses in the quest for therapeutics.

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The DC‐SIGN family member LSECtin is a novel ligand of CD44 on activated T cells

et al. 2010

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LSECtin, a novel member of the C-type lectin DC-SIGN family, not only acts as an attachment factor for pathogens, but also recognizes ''endogenous'' activated T cells. The endogenous ligands of LSECtin, however, have remained unclear. In this study, we identified CD44 on Jurkat T cells as a candidate ligand of LSECtin, and confirmed the specific interaction between LSECtin and CD44. Moreover, we showed that LSECtin selectively bound CD44s, CD44v4 and CD44v8-10 by screening a series of typical CD44 isoforms. By deletion of the carbohydrate-recognition domain region and mutation of crucial amino acids involved in carbohydrate-recognition of LSECtin and by inhibition of the N-linked glycosylation of CD44, we further demonstrated that the interaction between CD44 and LSECtin is dependent on protein-glycan recognition. Our findings indicate that CD44 is the first identified endogenous ligand of LSECtin, and similarly, that LSECtin is a novel ligand of CD44. These findings provide important new perspectives on the biology of both LSECtin and CD44 in the immune system. Supporting Information available online IntroductionThe C-type lectin DC-specific ICAM-grabbing non-integrin (SIGN) family clusters at chromosome 19p13.2 and includes CD23, DC-SIGN, L-SIGN and LSECtin [1,2]. It is well known that this family performs crucial functions in the innate immune response, as highlighted by the involvement of DC-SIGN in infection and dissemination of various pathogens, such as HIV, HCV and Mycobacterium tuberculosis [3][4][5]. Accumulating evidence suggests that the DC-SIGN family also contributes greatly to acquired immunity via recognition of endogenous ''self'' ligands. For example, DC-SIGN functions as a rolling receptor on DC to mediate transendothelial migration of DCs via ICAM-2 [6]. Moreover, DC-SIGN mediates strong adhesion between DC and resting T cells via ICAM-3 and is essential for DC-induced T-cell proliferation [7]. DC-SIGN-Mac-1-dependent interaction of DC with activated neutrophils modulates DC to promote a strong Th1 response [8]. CD23 is involved in both up-and downregulation of IgE via interaction with B-cell CD21 or IgE, respectively [9].The most recently identified member of the DC-SIGN family, LSECtin, has been detected on liver and lymph node sinusoidal endothelial cells at both the protein and RNA level [2]. LSECtin is also expressed in ex vivo isolated human peripheral blood and thymic DC as well as activated macrophages generated in vitro [10]. In addition, recent research SHORT COMMUNICATIONÃ These authors contributed equally to this work. Results and discussion CD44 on activated T cells is a candidate ligand of LSECtinIt has been shown that LSECtin recognizes activated Jurkat T cell lines and peripheral blood T cells (PBT). To identify the endogenous ligand of LSECtin, we performed immunoblot analysis on the Jurkat cell lysates treated with or without PMA and ionomycin with LSECtin-Fc. A 140-kD ligand and an 80-kD ligand specifically interact with LSECtin-Fc but not with controlFc (Fig. 1A). To inve...

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The DC-SIGN–related lectin LSECtin mediates antigen capture and pathogen binding by human myeloid cells

Cited by 86 publications

References 37 publications

The pathogen receptor liver and lymph node sinusoidal endotelial cell C-type lectin is expressed in human Kupffer cells and regulated by PU.1

The pathogen receptor liver and lymph node sinusoidal endotelial cell C-type lectin is expressed in human Kupffer cells and regulated by PU.1

Molecular Recognition in C‐Type Lectins: The Cases of DC‐SIGN, Langerin, MGL, and L‐Sectin

The DC‐SIGN family member LSECtin is a novel ligand of CD44 on activated T cells

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