C-type lectins on dendritic cells: key modulators for the induction of immune responses

2008 ◽  
Vol 36 (6) ◽  
pp. 1478-1481 ◽  
Author(s):  
Yvette van Kooyk
Keyword(s):  
Dendritic Cells ◽  
T Cell ◽  
Immune Responses ◽  
Cell Polarization ◽  
Cellular Interactions ◽  
Antigen Receptors ◽  
Lectin Receptors ◽  
Signalling Molecules ◽  
Intracellular Adhesion Molecule ◽  
Self Antigens

DCs (dendritic cells) are specialized in the recognition of pathogens and play a pivotal role in the control of immune responses. DCs are also important for homoeostatic control, recognizing self-antigens and tolerizing the tissue environment. The nature of the antigen recognized tilts the balance towards immunity or tolerance. CLRs (C-type lectin receptors) expressed by DC are involved in the recognition and capture of many glycosylated self-antigens and pathogens. It is now becoming clear that these CLRs may not only serve as antigen receptors allowing internalization and antigen presentation, but also function in the recognition of glycosylated self-antigens, and as adhesion and/or signalling molecules. The expression of C-type lectins is very sensitive to maturation stimuli, leading to down-regulation as DCs mature. CLRs such as DC-SIGN (DC-specific intracellular adhesion molecule-3 grabbing non-integrin) recognizes high-mannose-containing structures and Lewis antigens (Lex, Ley, Leb and Lea), whereas the CLR MGL (macrophage galactose/N-acetylgalactosamine-specific C-type lectin) recognizes GalNAc. Lex, Ley and GalNAc glycan structures are often expressed on tumours. We have demonstrated that glycan modification of antigen can strongly enhance MHC class I responses and the induction of antigen-specific cytotoxic T-lymphocytes, indicating that glycosylated antigen targets C-type lectin to enhance antigen-specific T-cell responses. Moreover, these CLRs induce signalling processes in DCs and specific cytokine responses in combination with TLR (Toll-like receptor) triggering. This implies that specific C-type lectin-targeted antigens can regulate T-cell polarization. Understanding the diversity of C-type lectins being expressed on DCs as well as their carbohydrate-specific recognition profiles should promote understanding of pathogen recognition in many diseases, as well as the regulation of cellular interactions of DCs that are essential in the control of immunity.

scholarly journals Dendritic Cells Promoted by Ginseng Saponins Drive a Potent Th1 Polarization

2008 ◽  
Vol 3 ◽  
pp. BMI.S585 ◽  
Author(s):  
Masao Takei ◽  
Eiichi Tachikawa ◽  
Akemi Umeyama
Keyword(s):  
T Cells ◽  
Dendritic Cells ◽  
T Cell ◽  
Immune Responses ◽  
Cell Polarization ◽  
Th1 Cells ◽  
Human Monocytes ◽  
Ifn Γ ◽  
Pharmacologically Active ◽  
Dc Maturation

Dendritic cells (DC) play a pivotal role in the initiation of T-cell-mediated immune responses, making them an attractive cellular adjuvant for use in cancer vaccines. The interaction of T cells with DC is crucial for directing T cell differentiation towards the Th1, Th2 or Th17 type, and several factors determining the direction of the T cell polarization. IL-12 plays a central role in the immune system, not only by augmenting the cytotoxic activity of T cells and NK cells and regulating IFN-γ production, but also by the capacity of IL-12 to promote the development of Th1 cells. Therefore, it is important to identify factors that might affect the differentiation, maturation and function of DC. Ginseng is a medicinal herb widely used in Asian countries, and many of its pharmacological actions are attributed to the ginsenosides. Moreover, T-cadinol and calamenene are sesquterpenes isolated from the heartwood of Cryptomeria japonica being pharmacologically active substances. We investigated whether M1 and M4, end products of steroidal ginseng saponins metabolized in digestive tracts, as well as T-cadinol and calamenene can drive DC maturation from human monocytes in vitro. Human monocytes were cultured with GM-CSF and IL-4 for 6 days under standard conditions, followed by another 2 days in the presence of M1, M4, T-cadinol or calamenene. The expression levels of CD1a, CD80, CD83, CD86 and HLA-DR on M1-primed DC, M4-primed DC, T-cadinol-primed DC and calamenene-primed DC were enhanced with a concomitant decrease in endocytic activity. M1-primed DC, M4-primed DC, T-cadinol-primed DC or calamenene-primed DC enhanced the T cell stimulatory capacity in an allo MLR (allogeneic mixed lymphocyte reaction). Naïve T cells co-cultured with allogeneic M1-primed DC, M4-primed DC, T-cadinol-primed DC or calamenene-primed DC turned into typical Th1 cells, which produced large quantities of IFN-γ and released small amounts of IL-4 depending on IL-12 secretion. In the CTL assay (cytotoxic T-lymphocyte assay), the production of IFN-γ and 51Cr release on M4-primed DC was more augmented than of immature DC or TNF-α-primed DC. These results suggest that M1, M4, T-cadinol and calamenene appear to be a good factor to induce DC maturation, or even better in some respect, for the use in clinical DC therapy to induce strong Th1 type immune responses.

scholarly journals In silico design of Phl p 6 variants with altered folding stability significantly impacts antigen processing, immunogenicity and immune polarization

2020 ◽  
Author(s):  
Petra Winter ◽  
Stefan Stubenvoll ◽  
Sandra Scheiblhofer ◽  
Isabella A Joubert ◽  
Lisa Strasser ◽  
...  
Keyword(s):  
Thermal Stability ◽  
Dendritic Cells ◽  
T Cell ◽  
Immune Responses ◽  
Point Mutations ◽  
Cell Polarization ◽  
T Cell Polarization ◽  
Fold Stability

AbstactIntroductionProtein fold stability has been proposed to represent an intrinsic feature contributing to immunogenicity and immune polarization by influencing the amount of peptide-MHC II complexes (pMHCII). Using in silico prediction, we introduced point mutations in proteins that either increase or decrease their fold-stability without altering immunodominant epitopes or changing the overall structure of the protein. Here, we investigated how modulation of the fold-stability of the grass pollen allergen Phl p 6 affects its ability to stimulate immune responses and T cell polarization.MethodsUsing the MAESTRO software tool, stabilizing or destabilizing mutations were selected and verified by molecular dynamics simulations. The mutants were expressed in E. coli, purified tag-free, and analyzed for thermal stability and resistance to endolysosomal proteases. The resulting peptides were analysed by degradome assay and mass spectrometry. The structure of the most stable mutant protein was obtained by X-ray crystallography. We evaluated the capacity of the mutants to stimulate T cell proliferation in vitro, as well as antibody responses and T cell polarization in vivo in an adjuvant-free BALB/c mouse model.ResultsFour stabilizing and two destabilizing mutations were identified by MAESTRO. Experimentally determined changes in thermal stability compared to the wild type protein ranged from -5 to +14 °C. Destabilization led to faster proteolytic processing in vitro, whereas highly stabilized mutants were degraded very slowly. However, the overall pattern of identified peptides remained very similar. This was confirmed in bone marrow derived dendritic cells that processed and presented the immune dominant epitope from a destabilized mutant more efficiently. In vivo, stabilization resulted in a shift in immune polarization as indicated by higher levels of IgG2a and increased secretion of TH1/TH17 cytokines.ConclusionMAESTRO was very efficient in detecting single point mutations that increase or reduce fold-stability. Thermal stability correlated well with susceptibility to protease resistance and presentation of pMHCII on the surface of dendritic cells in vitro. This change in processing kinetics significantly influenced the polarization of T cell responses in vivo. Modulating the fold-stability of proteins thus has the potential to optimize and polarize immune responses, which opens the door to more efficient design of molecular vaccines.

Immune Responses to Retinal Self-Antigens in CD25+CD4+Regulatory T-Cell–Depleted Mice

2004 ◽  
Vol 45 (6) ◽  
pp. 1879 ◽  
Author(s):  
Masaru Takeuchi ◽  
Hiroshi Keino ◽  
Takeshi Kezuka ◽  
Masahiko Usui ◽  
Osamu Taguchi
Keyword(s):  
T Cell ◽  
Immune Responses ◽  
Regulatory T Cell ◽  
Self Antigens

scholarly journals Rho-mDia1 pathway is required for adhesion, migration, and T-cell stimulation in dendritic cells

Blood ◽  
2010 ◽  
Vol 116 (26) ◽  
pp. 5875-5884 ◽  
Author(s):  
Hideaki Tanizaki ◽  
Gyohei Egawa ◽  
Kayo Inaba ◽  
Tetsuya Honda ◽  
Saeko Nakajima ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Dendritic Cells ◽  
T Cell ◽  
Immune Responses ◽  
Lymph Nodes ◽  
Actin Polymerization ◽  
Cell Stimulation ◽  
T Cell Stimulation ◽  
Acquired Immune Responses

Abstract Dendritic cells (DCs) are essential for the initiation of acquired immune responses through antigen acquisition, migration, maturation, and T-cell stimulation. One of the critical mechanisms in this response is the process actin nucleation and polymerization, which is mediated by several groups of proteins, including mammalian Diaphanous-related formins (mDia). However, the role of mDia in DCs remains unknown. Herein, we examined the role of mDia1 (one of the isoforms of mDia) in DCs. Although the proliferation and maturation of bone marrow-derived DCs were comparable between control C57BL/6 and mDia1-deficient (mDia1−/−) mice, adhesion and spreading to cellular matrix were impaired in mDia1−/− bone marrow–derived DCs. In addition, fluorescein isothiocyanate-induced cutaneous DC migration to draining lymph nodes in vivo and invasive migration and directional migration to CCL21 in vitro were suppressed in mDia1−/− DCs. Moreover, sustained T-cell interaction and T-cell stimulation in lymph nodes were impaired by mDia1 deficiency. Consistent with this, the DC-dependent delayed hypersensitivity response was attenuated by mDia1-deficient DCs. These results suggest that actin polymerization, which is mediated by mDia1, is essential for several aspects of DC-initiated acquired immune responses.

scholarly journals MONOCYTES, MACROPHAGES, DENDRITIC AND MYELOID SUPPRESSOR CELLS: GENESIS, CLASSIFICATION, IMMUNOBIOLOGICAL PROPERTIES

2018 ◽  
Vol 15 (3) ◽  
pp. 363-382
Author(s):  
L. P. Titov
Keyword(s):  
Dendritic Cells ◽  
T Cell ◽  
Immune Responses ◽  
Autoimmune Diseases ◽  
Suppressor Cells ◽  
Mononuclear Phagocyte ◽  
Natural Immunity ◽  
Myeloid Suppressor Cells ◽  
T Cell Immune Responses

The article presents the modern data on the most important component of natural immunity – cells of the mononuclear phagocyte system. The questions of origin, the spectrum of expressed markers of differentiation, the classification of monocytes (classical, intermediate, non-classical), macrophages (pro-inflammatory and anti-inflammatory) and dendritic cells (myeloid, plasmacytoid), their immunobiological functions, their role in humoral and T-cell immune responses, anergy and tolerance are considered. The possibility of obtaining cellular immunobiological products (adjuvant and tolerogenic) for immunotherapy of oncological, infectious and autoimmune diseases on their basis is analyzed.

scholarly journals Essential functions of Runx/Cbfβ in gut conventional dendritic cells for priming Rorγt+ T cells

2019 ◽  
Vol 3 (1) ◽  
pp. e201900441 ◽  
Author(s):  
Mari Tenno ◽  
Alicia Yoke Wei Wong ◽  
Mika Ikegaya ◽  
Eiji Miyauchi ◽  
Wooseok Seo ◽  
...  
Keyword(s):  
T Cells ◽  
Dendritic Cells ◽  
Immune Responses ◽  
Cell Polarization ◽  
Th Cells ◽  
Th Cell ◽  
Intrinsic Mechanism ◽  
Specific Effector ◽  
Acquired Immune Responses ◽  
Type 3

Acquired immune responses are initiated by activation of CD4+ helper T (Th) cells via recognition of antigens presented by conventional dendritic cells (cDCs). DCs instruct Th-cell polarization program into specific effector Th subset, which will dictate the type of immune responses. Hence, it is important to unravel how differentiation and/or activation of DC are linked with Th-cell–intrinsic mechanism that directs differentiation toward a specific effector Th subset. Here, we show that loss of Runx/Cbfβ transcription factors complexes during DC development leads to loss of CD103+CD11b+ cDC2s and alters characteristics of CD103−CD11b+ cDCs in the intestine, which was accompanied with impaired differentiation of Rorγt+ Th17 cells and type 3 Rorγt+ regulatory T cells. We also show that a Runx-binding enhancer in the Rorc gene is essential for T cells to integrate cDC-derived signals to induce Rorγt expression. These findings reveal that Runx/Cbfβ complexes play crucial and complementary roles in cDCs and Th cells to shape converging type 3 immune responses.

scholarly journals Nitric oxide dependent signaling via cyclic GMP in dendritic cells regulates migration and T-cell polarization

2018 ◽  
Vol 8 (1) ◽  
Author(s):  
Stefanie Gnipp ◽  
Evanthia Mergia ◽  
Michelle Puschkarow ◽  
Albrecht Bufe ◽  
Doris Koesling ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Dendritic Cells ◽  
T Cell ◽  
Cyclic Gmp ◽  
Cell Polarization ◽  
T Cell Polarization

scholarly journals CD5 on dendritic cells regulates CD4+ and CD8+ T cell activation and induction of immune responses

PLoS ONE ◽  
2019 ◽  
Vol 14 (9) ◽  
pp. e0222301 ◽  
Author(s):  
Hui Li ◽  
Erica Burgueño-Bucio ◽  
Shin Xu ◽  
Shaonli Das ◽  
Roxana Olguin-Alor ◽  
...  
Keyword(s):  
Dendritic Cells ◽  
T Cell ◽  
Immune Responses ◽  
T Cell Activation ◽  
Cell Activation ◽  
Cd8 T Cell

scholarly journals A simple self-adjuvanting biomimetic nanovaccine self-assembled with the conjugate of phospholipids and nucleotides can induce a strong cancer immunotherapeutic effect

2021 ◽  
Vol 9 (1) ◽  
pp. 84-92
Author(s):  
Dan Liu ◽  
Jiale Liu ◽  
Bing Ma ◽  
Bo Deng ◽  
Xigang Leng ◽  
...  
Keyword(s):  
Dendritic Cells ◽  
T Cell ◽  
Immune Responses ◽  
T Cell Responses ◽  
Cpg Odn ◽  
Cross Presentation ◽  
Cell Responses ◽  
Self Assembled ◽  
Cancer Immunotherapeutic

The biomimetic nanovaccines not only promoted antigens endocytosis into dendritic cells via receptor-mediated pathways but also induced antigens cross-presentation eliciting CD8+ T-cell responses. CPG-ODN as an adjuvant further enhanced the anti-tumor immune responses.

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