scholarly journals Nonneuronal Cholinergic System in Breast Tumors and Dendritic Cells: Does It Improve or Worsen the Response to Tumor?

2013 ◽  
Vol 2013 ◽  
pp. 1-12
Author(s):  
Marisa Vulcano ◽  
María Gabriela Lombardi ◽  
María Elena Sales
Keyword(s):  
Dendritic Cells ◽  
Cholinergic System ◽  
Parasympathetic Nervous System ◽  
Immune Cell ◽  
Breast Tumors ◽  
Cell Types ◽  
Cellular Functions ◽  
And Migration ◽  
And Function

Besides being the main neurotransmitter in the parasympathetic nervous system, acetylcholine (ACh) can act as a signaling molecule in nonneuronal tissues. For this reason, ACh and the enzymes that synthesize and degrade it (choline acetyltransferase and acetylcholinesterase) as well as muscarinic (mAChRs) and nicotinic receptors conform the non-neuronal cholinergic system (nNCS). It has been reported that nNCS regulates basal cellular functions including survival, proliferation, adhesion, and migration. Moreover, nNCS is broadly expressed in tumors and in different components of the immune system. In this review, we summarize the role of nNCS in tumors and in different immune cell types focusing on the expression and function of mAChRs in breast tumors and dendritic cells (DCs) and discussing the role of DCs in breast cancer.

scholarly journals Notch–RBP-J signaling controls the homeostasis of CD8− dendritic cells in the spleen

2007 ◽  
Vol 204 (7) ◽  
pp. 1653-1664 ◽  
Author(s):  
Michele L. Caton ◽  
Matthew R. Smith-Raska ◽  
Boris Reizis
Keyword(s):  
Target Gene ◽  
Immune Cell ◽  
Notch Pathway ◽  
Cell Types ◽  
Innate Immune ◽  
Receptor Ligands ◽  
Notch Receptors ◽  
And Function

Signaling through Notch receptors and their transcriptional effector RBP-J is essential for lymphocyte development and function, whereas its role in other immune cell types is unclear. We tested the function of the canonical Notch–RBP-J pathway in dendritic cell (DC) development and maintenance in vivo. Genetic inactivation of RBP-J in the bone marrow did not preclude DC lineage commitment but caused the reduction of splenic DC fraction. The inactivation of RBP-J in DCs using a novel DC-specific deleter strain caused selective loss of the splenic CD8− DC subset and reduced the frequency of cytokine-secreting CD8− DCs after challenge with Toll-like receptor ligands. In contrast, other splenic DC subsets and DCs in the lymph nodes and tissues were unaffected. The RBP-J–deficient splenic CD8− DCs were depleted at the postprogenitor stage, exhibited increased apoptosis, and lost the expression of the Notch target gene Deltex1. In the spleen, CD8− DCs were found adjacent to cells expressing the Notch ligand Delta-like 1 in the marginal zone (MZ). Thus, canonical Notch–RBP-J signaling controls the maintenance of CD8− DCs in the splenic MZ, revealing an unexpected role of the Notch pathway in the innate immune system.

scholarly journals Subsets of mononuclear phagocytes are enriched in the inflamed colons of patients with IBD

2019 ◽  
Vol 20 (1) ◽  
Author(s):  
Hong Liu ◽  
Suryasarathi Dasgupta ◽  
Yu Fu ◽  
Brandi Bailey ◽  
Christian Roy ◽  
...  
Keyword(s):  
Dendritic Cells ◽  
Disease Severity ◽  
Immune Cells ◽  
Immune Cell ◽  
Treatment Resistance ◽  
In Silico Analysis ◽  
Cell Types ◽  
Mononuclear Phagocyte ◽  
Mononuclear Phagocytes

Abstract Background Myeloid cells, especially mononuclear phagocytes, which include monocytes, macrophages and dendritic cells (DC), play vital roles in innate immunity, and in the initiation and maintenance of adaptive immunity. While T cell-associated activation pathways and cytokines have been identified and evaluated in inflammatory bowel disease (IBD) patients (Neurath, Nat Rev Gastroenterol Hepatol 14:269–78, 1989), the role of mononuclear phagocytes are less understood. Recent reports support the crucial role of DC subsets in the development of acute colitis models (Arimura et al., Mucosal Immunol 10:957–70, 2017), and suggest they may contribute to the pathogenesis of ulcerative colitis (UC) by inducing Th1/Th2/Th17 responses (Matsuno et al., Inflamm Bowel Dis 23:1524–34, 2017). Results We performed in silico analysis and evaluated the enrichment of immune cells, with a focus on mononuclear phagocytes in IBD patient colonic biopsies. Samples were from different gut locations, with different levels of disease severity, and with treatment response to current therapies. We observe enrichment of monocytes, M1 macrophages, activated DCs (aDCs) and plasmacytoid dendritic cells (pDCs) in inflamed tissues from various gut locations. This enrichment correlates with disease severity. Additionally, the same mononuclear phagocytes subsets are among the top enriched cell types in both infliximab and vedolizumab treatment non-responder samples. We further investigated the enrichment of selected DC and monocyte subsets based on gene signatures derived from a DC- and monocyte-focused single cell RNA-seq (scRNA-seq) study (Villani et al., Science 356:eaah4573, 2017), and verified enrichment in both inflamed tissues and those with treatment resistance. Moreover, we validated an increased mononuclear phagocyte subset abundance in a Dextran Sulphate Sodium (DSS) induced colitis model in C57Bl/6 mice representative of chronic inflammation. Conclusions We conducted an extensive analysis of immune cell populations in IBD patient colonic samples and identified enriched subsets of monocytes, macrophages and dendritic cells in inflamed tissues. Understanding how they interact with other immune cells and other cells in the colonic microenvironment such as epithelial and stromal cells will help us to delineate disease pathogenesis.

scholarly journals Lactate Is a Metabolic Mediator That Shapes Immune Cell Fate and Function

2021 ◽  
Vol 12 ◽  
Author(s):  
Heather L. Caslin ◽  
Daniel Abebayehu ◽  
Julia A. Pinette ◽  
John J. Ryan
Keyword(s):  
Cell Fate ◽  
Immune Cell ◽  
Cell Types ◽  
Cell Receptor ◽  
Substantial Impact ◽  
Specific Effects ◽  
Th 17 ◽  
Lactate Levels ◽  
And Function

Lactate and the associated H+ ions are still introduced in many biochemistry and general biology textbooks and courses as a metabolic by-product within fast or oxygen-independent glycolysis. However, the role of lactate as a fuel source has been well-appreciated in the field of physiology, and the role of lactate as a metabolic feedback regulator and distinct signaling molecule is beginning to gain traction in the field of immunology. We now know that while lactate and the associated H+ ions are generally immunosuppressive negative regulators, there are cell, receptor, mediator, and microenvironment-specific effects that augment T helper (Th)17, macrophage (M)2, tumor-associated macrophage, and neutrophil functions. Moreover, we are beginning to uncover how lactate and H+ utilize different transporters and signaling cascades in various immune cell types. These immunomodulatory effects may have a substantial impact in cancer, sepsis, autoimmunity, wound healing, and other immunomodulatory conditions with elevated lactate levels. In this article, we summarize the known effects of lactate and H+ on immune cells to hypothesize potential explanations for the divergent inflammatory vs. anti-inflammatory effects.

scholarly journals Biological characteristics of transcription factor RelB in different immune cell types: implications for the treatment of multiple sclerosis

2019 ◽  
Vol 12 (1) ◽  
Author(s):  
Meng-ge Yang ◽  
Li Sun ◽  
Jinming Han ◽  
Chao Zheng ◽  
Hudong Liang ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
T Cells ◽  
Dendritic Cells ◽  
Transcription Factor ◽  
Immune Cell ◽  
Demyelinating Disease ◽  
Cell Types ◽  
Lymphoid Organ ◽  
Therapeutic Implications

AbstractTranscription factor RelB is a member of the nuclear factror-kappa B (NF-κB) family, which plays a crucial role in mediating immune responses. Plenty of studies have demonstrated that RelB actively contributes to lymphoid organ development, dendritic cells maturation and function and T cells differentiation, as well as B cell development and survival. RelB deficiency may cause a variety of immunological disorders in both mice and humans. Multiple sclerosis (MS) is an inflammatory and demyelinating disease of the central nervous system which involves a board of immune cell populations. Thereby, RelB may exert an impact on MS by modulating the functions of dendritic cells and the differentiation of T cells and B cells. Despite intensive research, the role of RelB in MS and its animal model, experimental autoimmune encephalomyelitis, is still unclear. Herein, we give an overview of the biological characters of RelB, summarize the updated knowledge regarding the role of RelB in different cell types that contribute to MS pathogenesis and discuss the potential RelB-targeted therapeutic implications for MS.

The PI3K p110δ controls T-cell development, differentiation and regulation

2007 ◽  
Vol 35 (2) ◽  
pp. 167-171 ◽  
Author(s):  
D.T. Patton ◽  
F. Garçon ◽  
K. Okkenhaug
Keyword(s):  
T Cell ◽  
Cell Function ◽  
T Cell Development ◽  
Cell Development ◽  
Helper T Cells ◽  
Cellular Functions ◽  
Cellular And Humoral Immunity ◽  
And Migration ◽  
And Function

PI3Ks (phosphoinositide 3-kinases) regulate diverse cellular functions such as metabolism, growth, gene expression and migration. The p110δ isoform of PI3K is mainly expressed in cells of the immune system and contributes to cellular and humoral immunity. In the thymus, p110δ and p110γ play complementary roles in regulating the transition through key developmental checkpoints. In addition, p110δ regulates the differentiation of peripheral Th (helper T-cells) towards the Th1 and Th2 lineages. Moreover, p110δ is critical for Treg (regulatory T-cell) function. Here, we review the role of PI3Ks in T-cell development and function.

Role of the 807 C/T Polymorphism of the α2 Gene in Platelet GP Ia Collagen Receptor Expression and Function

1999 ◽  
Vol 81 (06) ◽  
pp. 951-956 ◽  
Author(s):  
J. Corral ◽  
R. González-Conejero ◽  
J. Rivera ◽  
F. Ortuño ◽  
P. Aparicio ◽  
...  
Keyword(s):  
Venous Thrombosis ◽  
Cell Types ◽  
Receptor Expression ◽  
Case Control Studies ◽  
Platelet Surface ◽  
Vitro Analysis ◽  
And Function ◽  
In Vitro Analysis

SummaryThe variability of the platelet GP Ia/IIa density has been associated with the 807 C/T polymorphism (Phe 224) of the GP Ia gene in American Caucasian population. We have investigated the genotype and allelic frequencies of this polymorphism in Spanish Caucasians. The T allele was found in 35% of the 284 blood donors analyzed. We confirmed in 159 healthy subjects a significant association between the 807 C/T polymorphism and the platelet GP Ia density. The T allele correlated with high number of GP Ia molecules on platelet surface. In addition, we observed a similar association of this polymorphism with the expression of this protein in other blood cell types. The platelet responsiveness to collagen was determined by “in vitro” analysis of the platelet activation and aggregation response. We found no significant differences in these functional platelet parameters according to the 807 C/T genotype. Finally, results from 3 case/control studies involving 302 consecutive patients (101 with coronary heart disease, 104 with cerebrovascular disease and 97 with deep venous thrombosis) determined that the 807 C/T polymorphism of the GP Ia gene does not represent a risk factor for arterial or venous thrombosis.

The paracaspase MALT1 in psoriasis

2021 ◽  
Vol 0 (0) ◽  
Author(s):  
Stephan Hailfinger ◽  
Klaus Schulze-Osthoff
Keyword(s):  
T Cells ◽  
Dendritic Cells ◽  
Transcription Factors ◽  
Skin Disease ◽  
Cell Types ◽  
Cytokine Receptors ◽  
Molecular Scaffold ◽  
Therapeutic Implications ◽  
Stimulation Of

Abstract Psoriasis is a frequent autoimmune-related skin disease, which involves various cell types such as T cells, keratinocytes and dendritic cells. Genetic variations, such as mutations of CARD14, can promote the development of the disease. CARD14 mutations as well as the stimulation of immune and cytokine receptors activate the paracaspase MALT1, a potent activator of the transcription factors NF-κB and AP-1. The disease-promoting role of MALT1 for psoriasis is mediated by both its protease activity as well as its molecular scaffold function. Here, we review the importance of MALT1-mediated signaling and its therapeutic implications in psoriasis.

scholarly journals Syndecans and Pancreatic Ductal Adenocarcinoma

Biomolecules ◽  
2021 ◽  
Vol 11 (3) ◽  
pp. 349
Author(s):  
Nausika Betriu ◽  
Juan Bertran-Mas ◽  
Anna Andreeva ◽  
Carlos E. Semino
Keyword(s):  
Extracellular Matrix ◽  
Pancreatic Ductal Adenocarcinoma ◽  
Cell Types ◽  
Ductal Adenocarcinoma ◽  
Physiological Processes ◽  
Extracellular Matrix Components ◽  
Detection And Diagnosis ◽  
And Migration ◽  
Early Detection And Diagnosis

Pancreatic Ductal Adenocarcinoma (PDAC) is a fatal disease with poor prognosis because patients rarely express symptoms in initial stages, which prevents early detection and diagnosis. Syndecans, a subfamily of proteoglycans, are involved in many physiological processes including cell proliferation, adhesion, and migration. Syndecans are physiologically found in many cell types and their interactions with other macromolecules enhance many pathways. In particular, extracellular matrix components, growth factors, and integrins collect the majority of syndecans associations acting as biochemical, physical, and mechanical transducers. Syndecans are transmembrane glycoproteins, but occasionally their extracellular domain can be released from the cell surface by the action of matrix metalloproteinases, converting them into soluble molecules that are capable of binding distant molecules such as extracellular matrix (ECM) components, growth factor receptors, and integrins from other cells. In this review, we explore the role of syndecans in tumorigenesis as well as their potential as therapeutic targets. Finally, this work reviews the contribution of syndecan-1 and syndecan-2 in PDAC progression and illustrates its potential to be targeted in future treatments for this devastating disease.

scholarly journals The Role of Immune Cell Types in Ischemic Heart Disease Progression: A Systematic Review

2021 ◽  
Vol 5 (10) ◽  
pp. 1-9
Author(s):  
Jenny Liu ◽  
Vaneeza Moosa ◽  
Isabelle Tan
Keyword(s):  
Systematic Review ◽  
Heart Disease ◽  
Ischemic Heart Disease ◽  
Disease Progression ◽  
Immune Cell ◽  
Cell Types ◽  
Ischemic Heart

scholarly journals Inhibition of O-GlcNAc Transferase Alters the Differentiation and Maturation Process of Human Monocyte Derived Dendritic Cells

Cells ◽  
2021 ◽  
Vol 10 (12) ◽  
pp. 3312
Author(s):  
Matjaž Weiss ◽  
Marko Anderluh ◽  
Martina Gobec
Keyword(s):  
Dendritic Cells ◽  
Posttranslational Modification ◽  
Human Monocyte ◽  
T Cell Differentiation ◽  
Maturation Process ◽  
Hla Dr ◽  
Glcnac Transferase ◽  
And Function

The O-GlcNAcylation is a posttranslational modification of proteins regulated by O-GlcNAc transferase (OGT) and O-GlcNAcase. These enzymes regulate the development, proliferation and function of cells, including the immune cells. Herein, we focused on the role of O-GlcNAcylation in human monocyte derived dendritic cells (moDCs). Our study suggests that inhibition of OGT modulates AKT and MEK/ERK pathways in moDCs. Changes were also observed in the expression levels of relevant surface markers, where reduced expression of CD80 and DC-SIGN, and increased expression of CD14, CD86 and HLA-DR occurred. We also noticed decreased IL-10 and increased IL-6 production, along with diminished endocytotic capacity of the cells, indicating that inhibition of O-GlcNAcylation hampers the transition of monocytes into immature DCs. Furthermore, the inhibition of OGT altered the maturation process of immature moDCs, since a CD14medDC-SIGNlowHLA-DRmedCD80lowCD86high profile was noticed when OGT inhibitor, OSMI-1, was present. To evaluate DCs ability to influence T cell differentiation and polarization, we co-cultured these cells. Surprisingly, the observed phenotypic changes of mature moDCs generated in the presence of OSMI-1 led to an increased proliferation of allogeneic T cells, while their polarization was not affected. Taken together, we confirm that shifting the O-GlcNAcylation status due to OGT inhibition alters the differentiation and function of moDCs in in vitro conditions.

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