scholarly journals The directed subdifferential of DC functions

2010 ◽  
pp. 27-43 ◽  
Author(s):  
Robert Baier ◽  
Elza Farkhi
Keyword(s):  
Dc Functions

Expression of Tyk2 in dendritic cells is required for IL-12, IL-23, and IFN-γ production and the induction of Th1 cell differentiation

Blood ◽  
2007 ◽  
Vol 110 (2) ◽  
pp. 553-560 ◽  
Author(s):  
Naoki Tokumasa ◽  
Akira Suto ◽  
Shin-ichiro Kagami ◽  
Shunsuke Furuta ◽  
Koichi Hirose ◽  
...  
Keyword(s):  
Dendritic Cells ◽  
Cell Differentiation ◽  
Cpg Odn ◽  
T Helper ◽  
Dc Functions ◽  
Th1 Cell ◽  
Th2 Cell ◽  
Ifn Γ ◽  
Antigen Presenting

Abstract It is well documented that dendritic cells (DCs), representative antigen-presenting cells, are important sources of Th1-promoting cytokines and are actively involved in the regulation of T-helper–cell differentiation. However, the intracellular event that regulates this process is still largely unknown. In this study, we examined the role of Tyk2, a JAK kinase that is involved in the signaling pathway under IL-12 and IL-23, in DC functions. While the differentiation and maturation of DCs was normal in Tyk2-deficient (Tyk2−/−) mice, IL-12–induced Stat4 phosphorylation was diminished in Tyk2−/− DCs. IL-12–induced IFN-γ production was also significantly diminished in Tyk2−/− DCs to levels similar to those in Stat4−/− DCs. Interestingly, Tyk2−/− DCs were defective in IL-12 and IL-23 production upon stimulation with CpG ODN. Furthermore, Tyk2−/− DCs were impaired in their ability to induce Th1-cell differentiation but not Th2-cell differentiation. Taken together, these results indicate that the expression of Tyk2 in DCs is crucial for the production of Th1-promoting cytokines such as IL-12 and IFN-γ from DCs and thereby for the induction of antigen-specific Th1-cell differentiation.

Trauma-hemorrhage inhibits splenic dendritic cell proinflammatory cytokine production via a mitogen-activated protein kinase process

2008 ◽  
Vol 294 (3) ◽  
pp. C754-C764 ◽  
Author(s):  
Takashi Kawasaki ◽  
Mashkoor A. Choudhry ◽  
Martin G. Schwacha ◽  
Satoshi Fujimi ◽  
James A. Lederer ◽  
...  
Keyword(s):  
Dendritic Cell ◽  
Cytokine Production ◽  
Mitogen Activated Protein Kinase ◽  
Sham Operation ◽  
Dc Functions ◽  
Mapk Activation ◽  
Midline Laparotomy ◽  
Shed Blood ◽  
Splenic Dendritic Cell ◽  
Mitogen Activated Protein

Although splenic dendritic cell (DC) functions are markedly altered following trauma-hemorrhage, the mechanism(s) responsible for the altered DC functions remains unknown. We hypothesized that trauma-hemorrhage inhibits DC function via suppressing toll-like receptor 4 (TLR4) expression and mitogen-activated protein kinases (MAPKs). To examine this, male C3H/HeN (6–8 wk) mice were randomly assigned to sham operation or trauma-hemorrhage. Trauma-hemorrhage was induced by midline laparotomy and ∼90 min of hypotension [blood pressure (BP) 35 mmHg], followed by fluid resuscitation (4× the shed blood volume in the form of Ringer lactate). Two hours later, mice were euthanized, splenic DCs were isolated, and the changes in their MAPK activation, TLR4-MD-2 expression, and ability to produce cytokines were measured. The results indicate that trauma-hemorrhage downregulated the lipopolysaccharide (LPS)-induced MAPK activation in splenic DCs. In addition to the decrease in MAPK activation, surface expression of TLR4-MD-2 was suppressed following trauma-hemorrhage. Furthermore, LPS-induced cytokine production from splenic DCs was also suppressed following trauma-hemorrhage. These findings thus suggest that the decrease in TLR4-MD-2 and MAPK activation may contribute to the LPS hyporesponsiveness of splenic DCs following trauma-hemorrhage. Hyporesponsiveness of splenic DCs was also found after stimulation with the TLR2 agonist zymosan. Our results may thus explain the profound immunosuppression that is known to occur under those conditions.

Farkas-type results for constrained fractional programming with DC functions

2014 ◽  
Vol 8 (8) ◽  
pp. 2299-2313 ◽  
Author(s):  
Xiang-Kai Sun ◽  
Yi Chai ◽  
Jing Zeng
Keyword(s):  
Fractional Programming ◽  
Dc Functions

scholarly journals Effect of interleukin-15 on depressed splenic dendritic cell functions following trauma-hemorrhage

2009 ◽  
Vol 296 (1) ◽  
pp. C124-C130 ◽  
Author(s):  
Takashi Kawasaki ◽  
Mashkoor A. Choudhry ◽  
Martin G. Schwacha ◽  
Kirby I. Bland ◽  
Irshad H. Chaudry
Keyword(s):  
Dendritic Cell ◽  
Antigen Presentation ◽  
Ex Vivo ◽  
Sham Operation ◽  
Dc Functions ◽  
Midline Laparotomy ◽  
Shed Blood ◽  
Cell Functions ◽  
Splenic Dendritic Cell ◽  
Ifn Γ

Although trauma-hemorrhage (T-H) induces suppressed splenic dendritic cell (DC) maturation and antigen presentation capacity, it remains unclear whether IL-15 modulates splenic DC functions. The aim of this study therefore was to investigate the effect of IL-15 on splenic DC functions after T-H. Male C3H/HeN mice (6–8 wk old) were randomly assigned to T-H or sham operation. T-H was induced by midline laparotomy and ∼90 min of hemorrhagic shock (blood pressure 35 mmHg), followed by fluid resuscitation (4× the shed blood volume in the form of Ringer lactate). Two hours later, mice were killed, splenic DCs were isolated, and the effects of exogenous IL-15 on their costimulatory factors, major histocompatibility class II expression, ability to produce cytokines, and antigen presentation were measured. The results indicate that IL-15 production capacity of splenic DCs was reduced following T-H. Ex vivo exposure to IL-15 attenuated the suppressed production of TNF-α, IL-6, and IFN-γ from splenic DCs following T-H. In addition, expression of surface antigen studies demonstrate that exogenous IL-15 attenuated T-H-induced downregulation of the activation of DC. The suppressed splenic DC antigen presentation function following T-H was also attenuated by IL-15 treatment. Moreover, IL-15 enhanced IL-12-induced IFN-γ production and antigen presentation by splenic DCs. These data suggest that ex vivo treatment with IL-15 following T-H provides beneficial effects on splenic DCs. The depression in IL-15 production by splenic DCs could contribute to the host's enhanced susceptibility to infections following T-H.

scholarly journals Metabolic Plasticity in Dendritic Cell Responses: Implications in Allergic Asthma

2017 ◽  
Vol 2017 ◽  
pp. 1-12 ◽  
Author(s):  
Amarjit Mishra
Keyword(s):  
Airway Inflammation ◽  
Lymphocyte Function ◽  
Dc Functions ◽  
Novel Treatments ◽  
Cellular Processes ◽  
Metabolic Plasticity ◽  
Cell Responses ◽  
Adaptive Immune ◽  
Current Review ◽  
Signaling Process

Dendritic cells (DCs) are highly specialized in antigen presentation and play a pivotal role in the initiation, progression, and perpetuation of adaptive immune responses. Emerging immune pathways are being recognized increasingly for DCs and their subsets that differentially regulate T lymphocyte function based on the type and interactions with the antigen. However, these interactions not only alter the signaling process and DC function but also render metabolic plasticity. The current review focuses on the metabolic cues of DCs that coordinate DC activation and differentiation and discuss whether targeting these fundamental cellular processes have implications to control airway inflammation and adaptive immunity. Therefore, strategies using metabolism-based therapeutic manipulation of DC functions could be developed into novel treatments for airway inflammation and asthma.

scholarly journals Tropomodulin1 Expression Increases Upon Maturation in Dendritic Cells and Promotes Their Maturation and Immune Functions

2021 ◽  
Vol 11 ◽  
Author(s):  
Xianmei Liu ◽  
Xue Xia ◽  
Xifu Wang ◽  
Jing Zhou ◽  
Lanping Amy Sung ◽  
...  
Keyword(s):  
Dendritic Cells ◽  
Actin Cytoskeleton ◽  
Costimulatory Molecules ◽  
Cell Stiffness ◽  
Actin Binding ◽  
Immune Functions ◽  
Dc Functions ◽  
Tlr4 Signaling ◽  
Functional Changes ◽  
Dc Maturation

Dendritic cells (DCs) are the most potent antigen-presenting cells. Upon maturation, DCs express costimulatory molecules and migrate to the lymph nodes to present antigens to T cells. The actin cytoskeleton plays key roles in multiple aspects of DC functions. However, little is known about the mechanisms and identities of actin-binding proteins that control DC maturation and maturation-associated functional changes. Tropomodulin1 (Tmod1), an actin-capping protein, controls actin depolymerization and nucleation. We found that Tmod1 was expressed in bone marrow-derived immature DCs and was significantly upregulated upon lipopolysaccharide (LPS)-induced DC maturation. By characterizing LPS-induced mature DCs (mDCs) from Tmod1 knockout mice, we found that compared with Tmod1+/+ mDCs, Tmod1-deficient mDCs exhibited lower surface expression of costimulatory molecules and chemokine receptors and reduced secretion of inflammatory cytokines, suggesting that Tmod1 deficiency retarded DC maturation. Tmod1-deficient mDCs also showed impaired random and chemotactic migration, deteriorated T-cell stimulatory ability, and reduced F-actin content and cell stiffness. Furthermore, Tmod1-deficient mDCs secreted high levels of IFN-β and IL-10 and induced immune tolerance in an experimental autoimmune encephalomyelitis (EAE) mouse model. Mechanistically, Tmod1 deficiency affected TLR4 signaling transduction, resulting in the decreased activity of MyD88-dependent NFκB and MAPK pathways but the increased activity of the TRIF/IRF3 pathway. Rescue with exogenous Tmod1 reversed the effect of Tmod1 deficiency on TLR4 signaling. Therefore, Tmod1 is critical in regulating DC maturation and immune functions by regulating TLR4 signaling and the actin cytoskeleton. Tmod1 may be a potential target for modulating DC functions, a strategy that would be beneficial for immunotherapy for several diseases.

scholarly journals The Human Mesenchymal Stromal Cell-Derived Osteocyte Capacity to Modulate Dendritic Cell Functions Is Strictly Dependent on the Culture System

2015 ◽  
Vol 2015 ◽  
pp. 1-10 ◽  
Author(s):  
Sara Trabanelli ◽  
Federico La Manna ◽  
Marco Romano ◽  
Valentina Salvestrini ◽  
Michele Cavo ◽  
...  
Keyword(s):  
Dendritic Cell ◽  
High Capacity ◽  
Host Immune System ◽  
Dc Functions ◽  
Routes Of Administration ◽  
Cell Functions ◽  
Osteogenic Cells ◽  
Different Types

In vitrodifferentiation of mesenchymal stromal cells (MSC) into osteocytes (human differentiated osteogenic cells, hDOC) before implantation has been proposed to optimize bone regeneration. However, a deep characterization of the immunological properties of DOC, including their effect on dendritic cell (DC) function, is not available. DOC can be used either as cellular suspension (detached, Det-DOC) or as adherent cells implanted on scaffolds (adherent, Adh-DOC). By mimickingin vitrothese two different routes of administration, we show that both Det-DOC and Adh-DOC can modulate DC functions. Specifically, the weak downregulation of CD80 and CD86 caused by Det-DOC on DC surface results in a weak modulation of DC functions, which indeed retain a high capacity to induce T-cell proliferation and to generate CD4+CD25+Foxp3+T cells. Moreover, Det-DOC enhance the DC capacity to differentiate CD4+CD161+CD196+Th17-cells by upregulating IL-6 secretion. Conversely, Adh-DOC strongly suppress DC functions by a profound downregulation of CD80 and CD86 on DC as well as by the inhibition of TGF-βproduction. In conclusion, we demonstrate that different types of DOC cell preparation may have a different impact on the modulation of the host immune system. This finding may have relevant implications for the design of cell-based tissue-engineering strategies.

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