Dendritic Cell-Associated Lectin-1: A Novel Dendritic Cell-Associated, C-Type Lectin-Like Molecule Enhances T Cell Secretion of IL-4

Ryan, Eleanor; Marshall, Aaron J.; Magaletti, Dario M.; Floyd, Helen; Draves, Kevin E.; Olson, N. Eric; Clark, Edward A.

doi:10.4049/jimmunol.169.10.5638

Cited by 73 publications

(51 citation statements)

References 47 publications

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“…B cells express a more limited repertoire of C-type lectins including CD23 (low affinity IgE receptor (42)), CD72 (43), CD69 (40), DC immunoreceptor (43), and DC-associated lectin-1 (41). Other than CD23, and possibly CD69, which have affinities for galactose (40,53), many of the ligands for these receptors have yet to be described.…”

Section: Discussionmentioning

confidence: 99%

Cryptococcus neoformans Glycoantigens Are Captured by Multiple Lectin Receptors and Presented by Dendritic Cells

Mansour

Latz

Levitz

2006

The Journal of Immunology

116

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Cell-mediated immune responses to glycoantigens have been largely uncharacterized. Protective T cell responses to the pathogenic yeast Cryptococcus neoformans are dependent on heavily mannosylated Ags termed mannoproteins. In the work presented, the innate immune response to mannoprotein was determined. Purified murine splenic dendritic cells (DC), B cells, and macrophages were used to stimulate mannoprotein-specific T cells. Only DC were capable of any measurable stimulation. Depletion of DC resulted in the abrogation of the T cell response. Human and murine DC rapidly captured fluorescent-labeled mannoprotein by a mannose receptor-mediated process. Using transfected cell lines, the type II C-type lectin receptor DC-specific ICAM-3-grabbing nonintegrin (CD209) was determined to have affinity for mannoprotein. Taken together with prior work demonstrating that mannoprotein was captured by the macrophage mannose receptor (CD206), these data suggest that multiple mannose receptors on DC recognize mannoprotein. Pulsing experiments demonstrated that DC captured sufficient mannoprotein over 2 h to account for 50% of total stimulation. Capture appeared dependent on mannose receptors, as competitive mannosylated inhibitors and calcium chelators each interfered with T cell stimulation. By confocal microscopy, intracellular mannoprotein trafficked to an endo-lysosomal compartment in DC, and at later time points extended into tubules in a similar fashion to the degradation marker DQ-OVA. Mannoprotein colocalized intracellularly with CD206 and CD209. These data suggest that DC provide the crucial link between innate and adaptive immune responses to C. neoformans via a process that is dependent upon the efficient uptake of mannoprotein by mannose receptors.

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Section: Discussionmentioning

confidence: 99%

Cryptococcus neoformans Glycoantigens Are Captured by Multiple Lectin Receptors and Presented by Dendritic Cells

Mansour

Latz

Levitz

2006

The Journal of Immunology

116

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“…Untouched monocytes were isolated from mononuclear cells by magnetic cell sorting (MACS) 15 (supplemental Figure II). The cells were suspended in Hanks balanced salt solution, 0.1% bovine serum albumin (HBSSA).…”

Section: Purification Of Recombinant Proteinsmentioning

confidence: 99%

High-Molecular-Weight Kininogen Fragments Stimulate the Secretion of Cytokines and Chemokines Through uPAR, Mac-1, and gC1qR in Monocytes

Khan

Bradford

Isordia‐Salas

et al. 2006

ATVB

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Objective-Plasma high-molecular-weight kininogen (HK) is cleaved in inflammatory diseases by kallikrein to HKa with release of bradykinin (BK). We postulated a direct link between HKa and cytokine/chemokine release. Methods and Results-HKa, but not BK, releases cytokines tumor necrosis factor (TNF)-␣, interleukin (IL)-1␤, IL-6, and chemokines IL-8 and MCP-1 from isolated human mononuclear cells. At a concentration of 600 nM, glutathione-Stransferase (GST) fusion proteins of kininogen domain 3 (D3), a fragment of domain 3, E7P (aaG255-Q292), HK domain 5 (D5), the D5 recombinant peptides HG (aa K420-D474) and HGK (aa H475-S626) stimulated secretion of IL-1␤ from mononuclear cells. Monoclonal antibodies (MAbs) specific for D5 or specific for D3 blocked release of IL-1␤ by HKa, supporting the importance of both domains. Antibodies to HK receptors on leukocytes including Mac-1, LFA-1, uPAR, and C1qR inhibited IL-1␤ secretion induced by tKa 98%, 89%, 85%, and 62%, respectively. Fractionation of mononuclear cells identified the responsible cell, a blood monocyte. Inhibitors of signaling pathways NFkB, JNK, and p38 but not extracellular signal-regulated kinase (ERK) decreased cytokine release from mononuclear cells. HKa increased the synthesis of IL-1␤ as deduced by an increase of IL-1␤ mRNA at 1 to 2 hours. Conclusions-HKa domains 3 and 5 may contribute to the pathogenesis of inflammatory diseases by releasing IL-1␤ from human monocytes using intracellular signaling pathways initiated by uPAR, ␤2 integrins and gC1qR. Key Words: chemokines Ⅲ cytokines Ⅲ kininogen Ⅲ monocytes Ⅲ uPAR F rom the discovery of kininogen, 1 the kallikrein-kinin system (KKS) has been intimately involved with inflammation. Plasma kallikrein cleaves HK to form BK and cleaved HK (HKa), which differs from HK because of major conformational changes. 2 BK increases capillary permeability by opening the tight junctions between endothelial cells and directly stimulates nerve endings causing pain, and is a potent vasodilator directly relaxing smooth muscles by releasing PGI 2 . The sum of these effects of BK reproduces many but not all aspects of inflammation. Emphasis in the past decade has shifted from contributions of HK to the humoral aspects of inflammation to its cellular participation, particularly interactions of HKa with leukocytes and endothelial cells. 3 Receptors on either or both of these cell types include selectins, which mediate leukocyte rolling and integrins, which mediate cell adhesion. Cellular proteases such as matrix metalloproteases degrade extracellular matrix protein in the basement membrane, facilitating neutrophil and mononuclear cell migration and emigration into tissues. The activation and participation of the KKS has been documented in inflammatory bowel disease 4 and arthritis 5 in rodents, which are models for human diseases such as rheumatoid arthritis and Crohns disease. Cytokines and chemokines released primarily but not exclusively from monocytes and tissue macrophages are known to play a central role in human inflamm...

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“…The majority of sequences corresponded to "named" genes present in the GenBank database and these included several B lymphocyte genes known to be up-regulated upon activation, such as Ig L chains, MHC class II, CD69, and RGS1/BL34 (Table I). Several novel genes were present among this initial set of sequences, one of which encodes Bam32, a novel CD40-inducible B lymphocyte signal transduction molecule that we have described elsewhere (51), and another which encodes a novel C-type lectin, DCAL-1 (64).…”

Section: Cloning and Sequence Analysis Of Fdc-spmentioning

confidence: 99%

FDC-SP, a Novel Secreted Protein Expressed by Follicular Dendritic Cells

Marshall

Draves

et al. 2002

The Journal of Immunology

Self Cite

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To define better the molecular basis for follicular dendritic cell (FDC) function, we used PCR-based cDNA subtraction to identify genes specifically expressed in primary FDC isolated from human tonsils. In this work we report the discovery of a novel gene encoding a small secreted protein, which we term FDC-SP (FDC secreted protein). The FDC-SP gene lies on chromosome 4q13 adjacent to clusters of proline-rich salivary peptides and C-X-C chemokines. Human and mouse FDC-SP proteins are structurally unique and contain a conserved N-terminal charged region adjacent to the leader peptide. FDC-SP has a very restricted tissue distribution and is expressed by activated FDCs from tonsils and TNF-α-activated FDC-like cell lines, but not by B cell lines, primary germinal center B cells, or anti-CD40 plus IL-4-activated B cells. Strikingly, FDC-SP is highly expressed in germinal center light zone, a pattern consistent with expression by FDC. In addition, FDC-SP is expressed in leukocyte-infiltrated tonsil crypts and by LPS- or Staphylococcus aureus Cowan strain 1-activated leukocytes, suggesting that FDC-SP can also be produced in response to innate immunity signals. We provide evidence that FDC-SP is posttranslationally modified and secreted and can bind to the surface of B lymphoma cells, but not T lymphoma cells, consistent with a function as a secreted mediator acting upon B cells. Furthermore, we find that binding of FDC-SP to primary human B cells is markedly enhanced upon activation with the T-dependent activation signals such as anti-CD40 plus IL-4. Together our data identify FDC-SP as a unique secreted peptide with a distinctive expression pattern within the immune system and the ability to specifically bind to activated B cells.

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Dendritic Cell-Associated Lectin-1: A Novel Dendritic Cell-Associated, C-Type Lectin-Like Molecule Enhances T Cell Secretion of IL-4

Cited by 73 publications

References 47 publications

Cryptococcus neoformans Glycoantigens Are Captured by Multiple Lectin Receptors and Presented by Dendritic Cells

Cryptococcus neoformans Glycoantigens Are Captured by Multiple Lectin Receptors and Presented by Dendritic Cells

High-Molecular-Weight Kininogen Fragments Stimulate the Secretion of Cytokines and Chemokines Through uPAR, Mac-1, and gC1qR in Monocytes

FDC-SP, a Novel Secreted Protein Expressed by Follicular Dendritic Cells

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