Dendritic cells (DCs) are crucial in the defense against pathogens and allergen. The ability of allergens to cause allergic inflammation is contingent upon the presence of microenvironment that either privileges Th2 responses or prohibits these reactions. As a simplification, this review tried to prove a causal relationship between a allergic disease and dendritic cell by satisfying the modified Koch's postulates. DCs express C-type lectin receptors (CLRs) and Toll like receptors (TLRs). DCs take up almost all allergen through CLRs. Uptake of allergen by CLRs leads to the production of anti-inflammatory reactions. Although both TLRs and CLRs have distinct functions, the balance between both receptors is instrumental for the immunological outcome.
Allergens ; Antigen-Presenting Cells ; Dendritic Cells* ; Inflammation ; Lectins, C-Type ; Toll-Like Receptors

Dendritic cells (DCs) are professional antigen-presenting cells capable of initiating and regulating innate and adaptive immunity. The development of effective ways to produce a large number of DCs in laboratories made the use of DCs available in various vaccine approaches. Compared to conventional vaccines, focused on protective antibody responses, DC vaccines emphasize protective T cell immunity but might elicit strong antibody responses as well. In addition, the recent discoveries of functionally distinct DC subsets in various organs and tissues are likely to increase the potential of exploiting DCs in vaccines and immunotherapy. Vaccines composed of DCs generated ex vivo, pulsed with antigens, and matured prior to being re-infused to the body have been widely tried clinically but resulted in limited success due to various obstacles. In this review, new approaches that protein vaccines are selectively targeted to the endocytic C-type lectin receptors on surface of DCs in vivo are discussed.
Adaptive Immunity ; Antibody Formation ; Antigen-Presenting Cells ; Dendritic Cells* ; Immunotherapy ; Lectins, C-Type* ; Receptors, Antigen ; Vaccines

OBJECTIVE: To investigate the in vivo intervention and relative mechanism of Genistein (GEN) on tumor-associated inflammatory and tumor thrombophilia in lymphoma-bearing mice. METHODS: Forty female Balb/c mice aged 5-6 weeks were injected with murine-derived Pro B-cell lymphoma cell line 38B9 to establish a lymphoma mouse model, which was randomly divided into control group, tumor-bearing group, GEN drug intervention group and cyclophosphamide (CTX）drug intervention group. Histopathologic was used to evaluate the tumorigenesis. Tumor formation was observed, and tumor tissues were collected of HE and immunohistochemical staining. ELISA and flow cytometry were used to detect the expression of inflammatory factors and the changes of thrombus indices in plasma after intervention of GEN and Cyclophosphamide (CTX) respectively. Immunohistochemistry method was used to detect the expression of CD19 in tomor tissues of tummor bearing mice. RESULTS: After 14 days of tumor bearing, the mice were tumorigenic. The lymphoma cells were diffusely distributed in the tumor tissue and the expression of CD19 in the tumor tissue was positive. The inflammatory factors such as IL-6, NETs and CLEC-2, and thrombotic indices such as TF, FIB and D-D in lymphoma-bearing mice were significantly higher than those before tumor-injection and lower than those after drug-intervention (all P<0.05). The levels of CLEC-2 and D-D in GEN group were significantly lower than those in CTX group (P<0.05). CONCLUSION Tumor-associated inflammation and thrombophilia exist in lymphoma-bearing mice. GEN shows better anti-inflammatory and anti-thrombotic effects compared with CTX by interfering with tumor inflammatory factors.
Mice ; Female ; Animals ; Genistein ; Lymphoma ; Cyclophosphamide ; Thrombophilia ; Inflammation ; Lectins, C-Type

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*

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

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*

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

OBJECTIVETo study the mechanism of oligochitosan-induced macrophage activation.

METHODSOligochitosan was chemically modified with fluorophore 2-aminoacridone (2-AMAC). The cellular events of 2-AMAC-oligochitosan-macrophage interaction were analyzed with confocal laser microscopy and the fluorescence intensity of cells was analyzed by BD LSR flow cytometer. The mechanism of oligochitosan uptake by macrophages was studied by competitive inhibition test and the effect of calcium, trypsin and colchicine on oligochitosan recognition and internalization were also determined. RT-PCR was performed to investigate the level of TNF-alpha secretion.

RESULTMacrophage could bind and uptake oligochitosan, which was dependent on the temperature: the uptake proceeded rapidly at 37 degrees C and at 4 degrees C macrophage could only bind oligochitosan. EDTA decreased oligochitosan uptake. Trypsin treatment significantly reduced the internalization, and uptake was recovered by trypsin termination. Colchicine significantly inhibited the internalization process and was dose dependent. 0.1 mol/L mannose inhibited TNF-alpha expression induced by oligochitosan.

CONCLUSIONMacrophage could uptake oligochitosan via mannose receptor mediated pinocytosis. Mannose receptor is crucial for the oligochitosan-induced macrophages activation.

Cells, Cultured ; Chitin ; analogs & derivatives ; pharmacology ; Humans ; Lectins, C-Type ; metabolism ; Macrophage Activation ; drug effects ; Macrophages ; cytology ; Mannose-Binding Lectins ; metabolism ; Pinocytosis ; drug effects ; Receptors, Cell Surface ; metabolism ; Tumor Necrosis Factor-alpha ; metabolism

AIMTo investigate the role of 1 alpha, 25-dihydroxyvitamin D3 (calcitriol) and its analogues tacalcitol and 24, 25(OH)2D3 on the phagocytosis of human monocyte-derived dendritic cells (MoDC).

METHODSMoDC were generated in vitro by differentiating monocytes in the presence of GM-CSF and IL-4 for 5 days. Expression of mannose receptor (MR) and Fc gamma receptors (Fc gamma Rs) by MoDC was analysed by flow cytometry. Zymosan ingestion was measured to assess the phagocytosis of MoDC.

RESULTSMoDC expressed high level of MR and Fc gamma Rs and showed the capacity of zymosan ingestion. Calcitriol and tacalcitol but no 24, 25(OH)2D3 not only upregulated the expression of MR and Fc gamma Rs on MoDC but also correspondingly enhanced their phagocytosis by increasing zymoasan ingestion. Furthermore, the upregulatory role occurred in the early stage of MoDC differentiation and was irreversible. The upregulatory role of calcitriol was dose dependent.

CONCLUSIONCalcitriol and its analogue tacalcitol may play an important role in dendritic cell binding and capturing foreign antigens at the initiation of immune response.

Calcitriol ; pharmacology ; Calcium Channel Agonists ; pharmacology ; Dendritic Cells ; drug effects ; metabolism ; physiology ; Dihydroxycholecalciferols ; pharmacology ; Humans ; Lectins, C-Type ; metabolism ; Mannose-Binding Lectins ; metabolism ; Monocytes ; cytology ; Phagocytosis ; drug effects ; Receptors, Cell Surface ; metabolism ; Receptors, IgG ; 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