C-type lectins (CTLs) represent a large family of soluble and membrane-bound proteins which bind calcium dependently via carbohydrate recognition domains (CRDs) to glycan residues presented on the surface of a variety of pathogens. The deconvolution of a cell's glycan code by CTLs underpins several important physiological processes in mammals such as pathogen neutralization and opsonization, leukocyte trafficking, and the inflammatory response. However, as our knowledge of CTLs has developed it has become apparent that the role of this innate immune family of proteins can be double-edged, where some pathogens have developed approaches to subvert and exploit CTL interactions to promote infection and sustain the pathological state. Equally, CTL interactions with host glycoproteins can contribute to inflammatory diseases such as arthritis and cancer whereby, in certain contexts, they exacerbate inflammation and drive malignant progression. This review discusses the 'dual agent' roles of some of the major mammalian CTLs in both resolving and promoting infection, inflammation and inflammatory disease and highlights opportunities and emerging approaches for their therapeutic modulation.
Animals ; Humans ; Inflammation/metabolism* ; Lectins, C-Type/metabolism* ; Mammals/metabolism* ; Membrane Proteins ; Polysaccharides/metabolism*

Lectins are proteins responsible for recognizing the signals of sugar molecules in the body. Sialic acid-binding immunoglobulin-like lectins (Siglecs) regulate the innate and adaptive immune responses in the tumor microenvironment by recognizing the glycan structure containing sialic acid and mediating downstream signals through immune receptor tyrosine inhibitory motifs. In recent years, a variety of tumor treatment strategies targeting the sialic acid-Siglecs axis have been introduced, including sialoglycoprotein-mediated drug delivery and antibody mediated inhibition of Siglecs from recognizing tumor surface ligands. In the future, by combining with glycoprotein nanotherapy, antibody therapy and gene therapy, Siglecs can be used to accurately locate tumor targets and release the anti-tumor immunity, so as to achieve the purpose of effective cure of tumors.
Sialic Acid Binding Immunoglobulin-like Lectins/metabolism* ; N-Acetylneuraminic Acid ; Immunoglobulins/metabolism* ; Receptors, Immunologic ; Ligands

Objective: To explore the development of a CAR-T cells targeting CLL-1 and verify its function. Methods: The expression levels of CLL-1 targets in cell lines and primary cells were detected by flow cytometry. A CLL-1 CAR vector was constructed, and the corresponding lentivirus was prepared. After infection and activation of T cells, CAR-T cells targeting CLL-1 were produced and their function was verified in vitro and in vivo. Results: CLL-1 was expressed in acute myeloid leukemia (AML) cell lines and primary AML cells. The transduction rate of the prepared CAR T cells was 77.82%. In AML cell lines and AML primary cells, CLL-1-targeting CAR-T cells significantly and specifically killed CLL-1-expressing cells. Compared to untransduced T cells, CAR-T cells killed target cells and secreted inflammatory cytokines, such as interleukin-6 and interferon-γ, at significantly higher levels (P<0.001) . In an in vivo human xenograft mouse model of AML, CLL-1 CAR-T cells also exhibited potent antileukemic activity and induced prolonged mouse survival compared with untransduced T cells [not reached vs 22 days (95%CI 19-24 days) , P=0.002]. Conclusion: CAR-T cells targeting CLL-1 have been successfully produced and have excellent functions.
Animals ; Cell Line, Tumor ; Cytokines ; Humans ; Immunotherapy, Adoptive ; Lectins, C-Type ; Leukemia, Myeloid, Acute/metabolism* ; Mice ; Receptors, Mitogen ; T-Lymphocytes

Sialic acid binding Ig-like lectin 10 (Siglec10) is a member of innate immune checkpoints that inhibits the activation of immune cells through the interaction with its ligand CD24 on tumor cells. Here, by analyzing public databases containing 64 517 patients of 33 cancer types, we found that the expression of Siglec10 was altered in 18 types of cancers and was associated with the clinical outcomes of 11 cancer types. In particular, Siglec10 was upregulated in patients with kidney renal clear cell carcinoma (KIRC) and was inversely associated with the prognosis of the patients. In 131 KIRC patients of our settings, Siglec10 was elevated in the tumor tissues of 83 (63.4%) patients compared with that in their counterpart normal kidney tissues. Moreover, higher level of Siglec10 was associated with advanced disease (stages III and IV) and worse prognosis. Silencing of CD24 in KIRC cells significantly increased the number of Siglec10-expressing macrophages phagocytosing KIRC cells. In addition, luciferase activity assays suggested that Siglec10 was a potential target of the transcription factors c-FOS and GATA1, which were identified by data mining. These results demonstrate that Siglec10 may have important oncogenic functions in KIRC, and represents a novel target for the development of immunotherapies.
Carcinoma, Renal Cell/pathology* ; Gene Expression Regulation, Neoplastic ; Humans ; Immunity, Innate ; Kidney Neoplasms/pathology* ; Lectins/metabolism* ; Prognosis ; Receptors, Cell Surface/metabolism*

The brain pericyte is a unique and indispensable part of the blood-brain barrier (BBB), and contributes to several pathological processes in traumatic brain injury (TBI). However, the cellular and molecular mechanisms by which pericytes are regulated in the damaged brain are largely unknown. Here, we show that the formation of neutrophil extracellular traps (NETs) induces the appearance of CD11b⁺ pericytes after TBI. These CD11b⁺ pericyte subsets are characterized by increased permeability and pro-inflammatory profiles compared to CD11b^- pericytes. Moreover, histones from NETs by Dectin-1 facilitate CD11b induction in brain pericytes in PKC-c-Jun dependent manner, resulting in neuroinflammation and BBB dysfunction after TBI. These data indicate that neutrophil-NET-pericyte and histone-Dectin-1-CD11b are possible mechanisms for the activation and dysfunction of pericytes. Targeting NETs formation and Dectin-1 are promising means of treating TBI.
Blood-Brain Barrier/metabolism* ; Brain/pathology* ; Brain Injuries, Traumatic/metabolism* ; Extracellular Traps/metabolism* ; Histones ; Humans ; Lectins, C-Type ; Pericytes/pathology*

OBJECTIVES: To study the expression of adipokines in children with primary nephrotic syndrome (PNS) before and after treatment and its correlation with blood lipids, as well as the role of adipokines in PNS children with hyperlipidemia. METHODS: A total of 90 children who were diagnosed with incipient PNS or recurrence of PNS after corticosteroid withdrawal for more than 6 months were enrolled as subjects. Thirty children who underwent physical examination were enrolled as the control group. Venous blood samples were collected from the children in the control group and the children with PNS before corticosteroid therapy (active stage) and after urinary protein clearance following 4 weeks of corticosteroid therapy (remission stage). ELISA was used to measure the levels of adipokines. An automatic biochemical analyzer was used to measure blood lipid levels. RESULTS: Compared with the control group, the children with PNS had a significantly lower level of omentin-1 in both active and remission stages, and their level of omentin-1 in the active stage was significantly lower than that in the remission stage ( CONCLUSIONS Omentin-1 may be associated with disease activity, dyslipidemia, and proteinuria in children with PNS. Blood lipid ratios may be more effective than traditional blood lipid parameters in monitoring early cardiovascular risk in children with PNS.
Adipokines ; Chemokines ; Child ; Cytokines/metabolism* ; GPI-Linked Proteins/metabolism* ; Humans ; Hyperlipidemias ; Lectins/metabolism* ; Lipids ; Nephrotic Syndrome/drug therapy* ; Proteinuria

Glycosylation is one of the common post-translational modifications of proteins to regulate the ability of tumor invasion, metastasis and tumor heterogeneity by interacting with glycan-binding proteins such as lectins and antibodies. Glycan microarray can be constructed by chemical synthesis, chemical-enzyme synthesis or natural glycan releasing. Glycan microarray is an essential analytical tool to discover the interaction between glycan and its binding proteins. Here we summarize the standard techniques to construct glycan microarray for the application in cancer vaccine, monoclonal antibody and diagnostic markers.
Antibodies, Monoclonal ; Glycosylation ; Lectins/metabolism* ; Microarray Analysis ; Neoplasms ; Polysaccharides

BACKGROUNDThe expression of dendritic cell-specific intercellular adhesion molecule 3-grabbing nonintegrin (DC-SIGN) in renal tubular epithelial cells has been thought to be highly correlated with the occurrence of several kidney diseases, but whether it takes place in renal tissues during hemorrhagic shock (HS) is unknown. The present study aimed to investigate this phenomenon and the inhibitory effect of Vitamin C (VitC).

METHODSA Sprague-Dawley rat HS model was established in vivo in this study. The expression level and location of DC-SIGN were observed in kidneys. Also, the degree of histological damage, the concentrations of tumor necrosis factor-μ and interleukin-6 in the renal tissues, and the serum concentration of blood urea nitrogen and creatinine at different times (2-24 h) after HS (six rats in each group), with or without VitC treatment before resuscitation, were evaluated.

RESULTSHS induced DC-SIGN expression in rat tubular epithelial cells. The proinflammatory cytokine concentration, histological damage scores, and functional injury of kidneys had increased. All these phenomena induced by HS were relieved when the rats were treated with VitC before resuscitation.

CONCLUSIONSThe results of the present study illustrated that HS could induce tubular epithelial cells expressing DC-SIGN, and the levels of proinflammatory cytokines in the kidney tissues improved correspondingly. The results also indicated that VitC could suppress the DC-SIGN expression in the tubular epithelial cells induced by HS and alleviate the inflammation and functional injury in the kidney.

Animals ; Ascorbic Acid ; therapeutic use ; Blotting, Western ; Cell Adhesion Molecules ; metabolism ; Epithelial Cells ; drug effects ; metabolism ; pathology ; Immunohistochemistry ; Kidney Tubules ; drug effects ; metabolism ; pathology ; Lectins, C-Type ; metabolism ; Male ; Rats ; Rats, Sprague-Dawley ; Receptors, Cell Surface ; metabolism ; Shock, Hemorrhagic ; complications ; drug therapy ; metabolism

OBJECTIVETo investigate the effect of low-selenium diet on the liver and kidneys of rats and explore the role of macrophage polarization into M1 and M2 phenotypes in liver and kidney injuries.

METHODSTwenty-four rats (12 female and 12 male) were randomly divided into control group and low-selenium group and fed with normal chow (dietary selenium of 0.18 mg/kg) and low-selenium diet (dietary selenium of 0.02 mg/kg) for 109 days. After the feeding, the rats were sacrificed for HE staining to observe liver and kidney pathologies, and immunohistochemistry was performed for analyzing CCR7, CD206, CD163-positive cell numbers in the liver and kidneys.

RESULTSThe rats in low-selenium group showed severer fibrosis in the liver and kidney than the control group. In either male or female rats in low-selenium group, CCR7 and CD206 expressions in the liver were comparable with those in control group, but CD163 expression was lower than that in the control group (P<0.05 for both female and male rats). In the kidney, the proximal tubule showed a slightly higher while the distal tubule showed a slightly lower CCR7 expression in low selenium group than in the control group (P>0.05). In low-selenium group, a significantly lower CD163 expression in the distal tubule and a significantly higher CD206 expression in the proximal tubule were noted as compared with the control group (P<0.05 in both female and male rats). Compared with the control rats, the male rats in low-selenium group, but not the female rats, showed a significantly lower CD163 expression in the proximal tubule of the kidney (P<0.05); the female but not the male rats in low-selenium group show a higher CD206 expression in the distal tubule (P<0.05).

CONCLUSIONLow-selenium diet can cause liver and kidney fibrosis in rats and may inhibit macrophage activation into the M2 phenotype.

Animals ; Antigens, CD ; metabolism ; Antigens, Differentiation, Myelomonocytic ; metabolism ; Diet ; Female ; Fibrosis ; Kidney ; metabolism ; pathology ; Lectins, C-Type ; metabolism ; Liver ; metabolism ; pathology ; Macrophage Activation ; Male ; Mannose-Binding Lectins ; metabolism ; Rats ; Receptors, CCR7 ; metabolism ; Receptors, Cell Surface ; metabolism ; Selenium ; administration & dosage

Polymeric micelles have exhibited attractive properties as drug carriers, such as high stability in vivo and good biocompatibility, and been successfully used to dissolve various drugs of poor aqueous solubilities. In this study, we developed a new type of polymeric micelles with mannose-mediated targeting and pH-responsive drug release properties for anticancer drug delivery. The polymeric micelles were prepared from an amphiphilic polymer, poly (glycidyl methacrylate)-g-mannose (PGMA-Mannose). An anticancer drug, doxorubicin (DOX), was encapsulated into the micelles during the micellization, and could be released rapidly under acidic condition. The specificity of cellular uptake of the micelles by two different cell lines was studied using confocal laser scanning microscopy and the MTT assay. DOX-loaded micelles were efficiently trapped by mannose-receptor-overexpressing cancer cells MDA-MB-231, whereas mannose- receptor-poor cells HEK293 showed much lower endocytosis towards the micelles under the same conditions. Thus, DOX-loaded micelles displayed higher cytotoxicity to MDA-MB-231 cancer cells as compared with free DOX. The present study demonstrates that PGMA-Mannose micelles are a promising targeted drug delivery system for cancer therapy.
Cell Line, Tumor ; Doxorubicin ; pharmacology ; Drug Delivery Systems ; HEK293 Cells ; Humans ; Lectins, C-Type ; metabolism ; Mannose ; chemistry ; Mannose-Binding Lectins ; metabolism ; Micelles ; Receptors, Cell Surface ; metabolism