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Topic Review
Immunomodulation by Gut Microbiome on Gastrointestinal Cancers
Gastrointestinal cancer (GI) is a global health disease with a huge burden on a patient’s physical and psychological aspects of life and on health care providers. It is associated with multiple disease related challenges which can alter the patient’s quality of life and well-being. GI cancer development is influenced by multiple factors such as diet, infection, environment, and genetics. Although activating immune pathways and components during cancer is critical for the host’s survival, cancerous cells can target those pathways to escape and survive. As the gut microbiome influences the development and function of the immune system, research is conducted to investigate the gut microbiome–immune interactions, the underlying mechanisms, and how they reduce the risk of GI cancer. 
  • 700
  • 06 May 2022
Topic Review
Germinal Centers in Rheumatoid Arthritis
Rheumatoid Arthritis (RA) is a chronic autoimmune disease characterized by joint inflammation, affecting approximately 1% of the general population. To alleviate symptoms and ameliorate joint damage, chronic use of immunosuppressives is needed. However, these treatments are only partially effective and may lead to unwanted side effects. Therefore, a more profound understanding of the pathophysiology might lead to more effective therapies, or better still, a cure.  The presence of autoantibodies in RA indicates that B-cells might have a pivotal role in the disease. This concept is further supported by the fact that a diverse antibody response to various arthritis related epitopes is associated with arthritis development. In this context, attention has focused in recent years on the role of Germinal Centers (GCs) in RA. Since GCs act as the main anatomic location of somatic hypermutations, and thus contribute to the diversity and specificity of (auto) antibodies, it has been speculated that defects in germinal center reactions might be crucial in the initiation and maintenance of auto-immune events.
  • 698
  • 27 Oct 2021
Topic Review
B7 Molecules on Dendritic Cells after LPS Stimulation
A key aspect of the inflammatory phenomenon is the involvement of costimulatory molecules expressed by antigen-presenting cells (APCs) and their ability to secrete cytokines to set instructions for adaptive immune response and to generate tolerance or inflammation. In a novel integrative approach, the evaluation of the kinetic expression of the membrane and soluble B7 costimulatory molecules CD86, ICOS-L, PDL1, PDL2 was presented, the transcription factor Interferon Regulatory Factor 4 (IRF4), and the cytokines produced by monocyte-derived dendritic cells (Mo-DCs) after challenging them with different concentrations of stimulation with E. coli lipopolysaccharide (LPS) for various lengths of time. The evaluation showed that the stimuli concentration and time of exposure to LPS are critical factors in modulating the dynamic expression pattern of membrane and soluble B7 molecules and cytokines.
  • 698
  • 11 Aug 2022
Topic Review
Complement–Sphingolipid System in COVID-19 and Gaucher Diseases
Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2)-induced disease (COVID-19) and Gaucher disease (GD) exhibit upregulation of complement 5a (C5a) and its C5aR1 receptor, and excess synthesis of glycosphingolipids that lead to increased infiltration and activation of innate and adaptive immune cells, resulting in massive generation of pro-inflammatory cytokines, chemokines and growth factors. This C5a–C5aR1–glycosphingolipid pathway- induced pro-inflammatory environment causes the tissue damage in COVID-19 and GD. Strikingly, pharmaceutically targeting the C5a–C5aR1 axis or the glycosphingolipid synthesis pathway led to a reduction in glycosphingolipid synthesis and innate and adaptive immune inflammation, and protection from the tissue destruction in both COVID-19 and GD. 
  • 698
  • 29 Nov 2022
Topic Review
Natural Killer Cells in Immunotherapy
Here, the last pre-clinical and clinical studies published in the last five years where natural killer (NK) cells have been administered as an immunotherapy option for the treatment of cancer patients. Author describe studies administering NK cells alone and in combination with monoclonal antibodies that either promote antibody-dependent cell cytotoxicity or block immune checkpoint receptors. They review the use of genetically modified NK cells including chimeric antigen receptor (CAR)-modified NK cells and other modifications that can enhance the anti-tumor activity of NK cells. Moreover, author describe studies related to the antimicrobial activity of NK cells as we believe they demonstrate important lessons that we can learn and apply to improve the anti-tumor activity of NK cells. All these studies are described with the aim to find tips to improve the success of NK cells as an immunotherapy option in cancer patients.
  • 697
  • 05 Nov 2020
Topic Review
CAR T-Cells in the Treatment of Solid Tumors
Chimeric antigen receptor (CAR) T-cell therapy is a newly designed adoptive immunotherapy that is able to target and further eliminate cancer cells by engaging with MHC-independent tumor-antigens. CAR T-cell therapy has exhibited conspicuous clinical efficacy in hematological malignancies, but more than half of patients will relapse.  
  • 692
  • 16 Dec 2022
Topic Review
Joint-Preserving Surgery
The concept of “joint-preservation” was introduced by Hanyu et al. in 1997. They started joint-preserving surgery to preserve the function of the MTP joints as they recognized its function as important for gait even in patients with RA.
  • 691
  • 23 Apr 2021
Topic Review
Manipulating Microbiota to Treat Atopic Dermatitis
Atopic dermatitis (AD) is a globally prevalent skin inflammation with a particular impact on children. Current therapies for AD are challenged by the limited armamentarium and the high heterogeneity of the disease. Thus, radically different approaches are needed to address a significant unmet need in AD patients. A novel promising therapeutic target for AD is the microbiota.
  • 691
  • 13 Jun 2022
Topic Review
Innate Immune Receptor Stimulation
Immunometabolism is a relatively new field of research that aims at understanding interconnections between the immune system and cellular metabolism. This is now well-documented for innate immune cells of the myeloid lineage such as macrophages and myeloid dendritic cells (DCs) when they engage their differentiation or activation programs. Several studies have shown that stimulation of DCs or macrophages by the binding of pathogen-associated molecular patterns (PAMPs) to pattern recognition receptors (PRRs) leads to increased glycolytic activity and rewiring of central carbon metabolism. These metabolic modulations are essential to support and settle immunological functions by providing energy and immunoregulatory metabolites. As the understanding of molecular mechanisms progressed, significant differences between cell types and species have also been discovered. Pathways leading to the regulation of central carbon metabolism in macrophages and DCs by PRR signaling and consequences on cellular functions are reviewed here.
  • 690
  • 08 Feb 2021
Topic Review
Combination Antibody Therapy against Pseudomonas aeruginosa Infections
Despite advances in antimicrobial therapy and even the advent of some effective vaccines, Pseudomonas aeruginosa (P. aeruginosa) remains a significant cause of infectious disease, primarily due to antibiotic resistance. Although P. aeruginosa is commonly treatable with readily available therapeutics, these therapies are not always efficacious, particularly for certain classes of patients (e.g., cystic fibrosis (CF)) and for drug-resistant strains. Combinations of monoclonal antibodies against different targets and epitopes have demonstrated synergistic efficacy with each other as well as in combination with antimicrobial agents typically used to treat these infections. Such a strategy has reduced the ability of infectious agents to develop resistance. This entry highlights potential targets secreted by P. aeruginosa that future polyclonal antibodies may directed against in order to develop more efficacious treatments against these infections. 
  • 689
  • 06 Jan 2022
Topic Review
Specialized Pro-Resolving Mediators Biomarkers
The application of precision medicine paradigm in the daily treatment of patients has been greatly hampered by the lack of robust biomarkers. Lipid mediators are central in the regulation of host immune responses during both the initiation and resolution of inflammation. Amongst lipid mediators, the specialized pro-resolving mediators (SPM) govern immune cells to promote the resolution of inflammation. These autacoids are produced via the stereoselective conversion of essential fatty acids to yield molecules that are dynamically regulated during inflammation and exert potent immunoregulatory activities. Furthermore, there is an increasing appreciation for the role that these mediators play in conveying the biological actions of several anti-inflammatory therapeutics. Identification and quantitation of these mediators has traditionally been achieved using hyphenated mass spectrometric techniques, primarily liquid-chromatography tandem mass spectrometry. 
  • 685
  • 03 Mar 2022
Topic Review
Cytoplasmic Functions of cIAP1
Cellular inhibitor of apoptosis 1 (cIAP1) is a cell signaling regulator of the IAP family. Through its E3-ubiquitine ligase activity, it has the ability to activate intracellular signaling pathways, modify signal transduction pathways by changing protein-protein interaction networks, and stop signal transduction by promoting the degradation of critical components of signaling pathways. Thus, cIAP1 appears to be a potent determinant of the response of cells, enabling their rapid adaptation to changing environmental conditions or intra- or extracellular stresses. It is expressed in almost all tissues, found in the cytoplasm, membrane and/or nucleus of cells. cIAP1 regulates innate immunity by controlling signaling pathways mediated by tumor necrosis factor receptor superfamily (TNFRs), some cytokine receptors and pattern recognition-receptors (PRRs). Although less documented, cIAP1 has also been involved in the regulation of cell migration and in the control of transcriptional programs. 
  • 684
  • 18 Mar 2022
Topic Review
Tumor Necrosis Factor-α
Tumor necrosis factor-α (TNF-α) is a pleiotropic cytokine expressed by macrophages, monocytes, and T cells, and its expression is triggered by the immune system in response to pathogens and their products, such as endotoxins. TNF-α plays an important role in host defense by inducing inflammatory reactions such as phagocytes and cytocidal systems activation. TNF-α also plays an important role in bone metabolism and is associated with inflammatory bone diseases. TNF-α binds to two cell surface receptors, the 55kDa TNF receptor-1 (TNFR1) and the 75kDa TNF receptor-2 (TNFR2).
  • 684
  • 11 Mar 2022
Topic Review
Nanoparticle- and Microparticle-Based Vaccines against Orbiviruses
Bluetongue virus (BTV) and African horse sickness virus (AHSV) are widespread arboviruses that cause important economic losses in the livestock and equine industries, respectively. In addition to these, another arthropod-transmitted orbivirus known as epizootic hemorrhagic disease virus (EHDV) entails a major threat as there is a conducive landscape that nurtures its emergence in non-endemic countries. To date, only vaccinations with live attenuated or inactivated vaccines permit the control of these three viral diseases, although important drawbacks, e.g., low safety profile and effectiveness, and lack of DIVA (differentiation of infected from vaccinated animals) properties, constrain their usage as prophylactic measures. Moreover, a substantial number of serotypes of BTV, AHSV and EHDV have been described, with poor induction of cross-protective immune responses among serotypes. In the context of next-generation vaccine development, antigen delivery systems based on nano- or microparticles have gathered significant attention. A diversity of technologies, such as virus-like particles or self-assembled protein complexes, have been implemented for vaccine design against these viruses.
  • 681
  • 19 Jul 2022
Topic Review
Sepsis and HMGB1 Release
Sepsis remains a common cause of death in intensive care units, accounting for approximately 20% of total deaths worldwide. Its pathogenesis is partly attributable to dysregulated inflammatory responses to bacterial endotoxins (such as lipopolysaccharide, LPS), which stimulate innate immune cells to sequentially release early cytokines (such as tumor necrosis factor (TNF) and interferons (IFNs)) and late mediators (such as high-mobility group box 1, HMGB1).  Below is a brief summary of the intricate mechanisms underlying the regulation of bacterial endotoxin-induced HMGB1 release.
  • 678
  • 13 Sep 2021
Topic Review
Effects of Oxysterols on Immune Cells
Oxysterols are the products of cholesterol oxidation. They have a wide range of effects on several cells, organs, and systems in the body. Oxysterols also have an influence on the physiology of the immune system, from immune cell maturation and migration to innate and humoral immune responses. 
  • 678
  • 21 Apr 2022
Topic Review
Immunosurveillance and Immunoediting
The mechanisms by which immune systems identify and destroy tumors, known as immunosurveillance, have been discussed for decades. However, several factors that lead to tumor persistence and escape from the attack of immune cells in a normal immune system have been found. In the process known as immunoediting, tumors decrease their immunogenicity and evade immunosurveillance. Furthermore, tumors exploit factors such as regulatory T cells, myeloid-derived suppressive cells, and inhibitory cytokines that avoid cytotoxic T cell (CTL) recognition. 
  • 671
  • 13 Feb 2023
Topic Review
CD4 T-Cell in Inflammatory Bowel Disease
Inflammatory bowel disease (IBD) is an umbrella term for the chronic immune-mediated idiopathic inflammation of the gastrointestinal tract, manifesting as Crohn’s disease (CD) or ulcerative colitis (UC). IBD is characterized by exacerbated innate and adaptive immunity in the gut in association with microbiota dysbiosis and the disruption of the intestinal barrier, resulting in increased bacterial exposure. In response to signals from microorganisms and damaged tissue, innate immune cells produce inflammatory cytokines and factors that stimulate T and B cells of the adaptive immune system, and a prominent characteristic of IBD patients is the accumulation of inflammatory T-cells and their proinflammatory-associated cytokines in intestinal tissue. Upon antigen recognition and activation, CD4 T-cells differentiate towards a range of distinct phenotypes: T helper(h)1, Th2, Th9, Th17, Th22, T follicular helper (Tfh), and several types of T-regulatory cells (Treg). T-cells are generated according to and adapt to microenvironmental conditions and participate in a complex network of interactions among other immune cells that modulate the further progression of IBD. 
  • 670
  • 09 Feb 2023
Topic Review
Extracellular Vesicles in Osteoarthritis
Along with cytokines, extracellular vesicles (EVs) released by immune cells in the joint contribute to osteoarthritis (OA) pathogenesis. By high-resolution flow cytometry, we characterized 18 surface markers and 4 proinflammatory cytokines carried by EVs of various sizes in plasma and synovial fluid (SF) from individuals with knee OA, with a primary focus on immune cells that play a major role in OA pathogenesis.
  • 668
  • 09 Sep 2021
Topic Review
Multiplex Tissue Imaging
Multiplex spatial analysis methods have recently been developed; these have offered insight into how cellular crosstalk dynamics and heterogeneity affect cancer prognoses and responses to treatment. Multiplex (imaging) technologies and computational analysis methods allow for the spatial visualization and quantification of cell–cell interactions and properties. These technological advances allow for the discovery of cellular interactions within the tumor microenvironment and provide detailed single-cell information on properties that define cellular behavior.
  • 666
  • 08 Jul 2022
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