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Tailored Modulation of Cellular Pro-inflammatory Responses With Disaccharide Lipid A Mimetics
We report on controllable modulation of cellular pro-inflammatory responses by application of novel synthetic glycolipids—disaccharide-based lipid A mimetics (DLAMs) having picomolar affinity for TLR4/MD-2. Using crystal structure inspired design we have developed endotoxin mimetics where the inherently flexible β(1 → 6)-linked diglucosamine backbone of lipid A is replaced by a conformationally restricted α,α-(1↔1)-linked disaccharide scaffold. The tertiary structure of the disaccharide skeleton of DLAMs mirrors the 3-dimensional shape of TLR4/MD-2 bound E. coli lipid A. Due to exceptional conformational rigidity ...
Source: Frontiers in Immunology - March 18, 2021 Category: Allergy & Immunology Source Type: research

Current Clinical Trials in Pemphigus and Pemphigoid
Conclusions The clinical trials discussed here, which include several trials investigating novel therapeutic targets, demonstrate that translational research in pemphigus and pemphigoid is a fast-growing field. We thus expect that several novel treatments will be shortly available for the treatment of pemphigus and pemphigoid patients. Given the high, and thus far unmet, medical need in this field (110), this is highly encouraging and will hopefully improve the quality of life of the affected patients. In addition to the compounds and targets described here, several new targets have been recently identified in preclinical...
Source: Frontiers in Immunology - May 2, 2019 Category: Allergy & Immunology Source Type: research

Myeloid-Derived Suppressor Cells: Ductile Targets in Disease
Discussion MDSCs violently emerge in pathological conditions in an attempt to limit potentially harmful immune and inflammatory responses. Mechanisms supporting their expansion and survival are deeply investigated in cancer, in the perspective to reactivate specific antitumor responses and prevent their contribution to disease evolution. These findings will likely contribute to improve the targeting of MDSCs in anticancer immunotherapies, either alone or in combination with immune checkpoint inhibitors. New evidence indicates that the expansion of myeloid cell differentiation in pathology is subject to fine-tuning, as its...
Source: Frontiers in Immunology - May 2, 2019 Category: Allergy & Immunology Source Type: research

Blocking IL-19 Signaling Ameliorates Allergen-Induced Airway Inflammation
This study was carried out in accordance with the recommendations of the National Institutes of Health standards and guidelines for the care and use of experimental animals. The protocol was approved by the Animal Ethics Committee of National Cheng Kung University (IACUC NO. 107272 and 105077). Author Contributions J-YW and M-SC designed the study. Y-HW and Y-LL performed the experiments. Y-HW and W-YC analyzed the data. Y-HW, W-YC, and M-SC wrote the manuscript. W-YC and J-YW provided critical technical and scientific guidance and discussion. Funding This work was supported by research grant from the Ministry of Scien...
Source: Frontiers in Immunology - April 29, 2019 Category: Allergy & Immunology Source Type: research

Leukocyte Heparanase: A Double-Edged Sword in Tumor Progression
Conclusions This review describes how leukocyte-heparanase can be a double-edged sword in tumor progression; it can enhance tumor immune surveillance and tumor cell clearance, but also promote tumor survival and growth. We also discuss the potential of using heparanase in leukocyte therapies against tumors, and the effects of heparanase inhibitors on tumor progression and immunity. We are just beginning to understand the influence of heparanase on a pro/anti-tumor immune response, and there are still many questions to answer. How do the pro/anti-tumorigenic effects of heparanase differ across different cancer types? Does...
Source: Frontiers in Oncology - April 29, 2019 Category: Cancer & Oncology Source Type: research

T Cell Receptor Expression Timing and Signal Strength in the Functional Differentiation of Invariant Natural Killer T Cells
Nyambayar Dashtsoodol1,2*, Sabrina Bortoluzzi1 and Marc Schmidt-Supprian1* 1Department of Hematology and Medical Oncology, Klinikum rechts der Isar and TranslaTUM Cancer Center, Technische Universität München, München, Germany 2Department of Microbiology and Immunology, School of Biomedicine, Mongolian National University of Medical Sciences, Ulaanbaatar, Mongolia The CD1d-restricted Vα14 invariant NKT (iNKT) cell lineage in mice (Vα24 in humans) represents an evolutionary conserved innate-like immune cell type that recognizes glycolipid antigens. Because of their unique a...
Source: Frontiers in Immunology - April 25, 2019 Category: Allergy & Immunology Source Type: research

Core Gut Bacteria Analysis of Healthy Mice
Conclusion In conclusion, our results exhibited a relatively complete picture of core gut bacteria in healthy mice that they were mainly composed of carbohydrate- and amino acids-metabolizing bacteria and immunomodulatory bacteria, as well as their ecological relationships of symbiosis or functional redundancy. It was worth noting that the core bacteria resident in healthy gut was of fundamental importance for not only the healthy physiological characteristics, but also the chronic metabolic disease phenotypes. Our study focused on the gut microbiota of healthy host, and would be an important complement to the case–...
Source: Frontiers in Microbiology - April 23, 2019 Category: Microbiology Source Type: research

Oligonucleotides —A Novel Promising Therapeutic Option for IBD
Conclusions In this review, we focused on recent and past approaches to test the therapeutic efficacy of oligonucleotide based therapies in IBD. The combining mechanistic mode of oligonucleotide based therapeutics is a targeted action on specific pro-inflammatory molecules, which are over activated in IBD patients and contribute significantly to disease pathogenesis. The proposed high selectivity of the agents is derived from its mode of action, that aims to specifically block certain inflammatory molecular patterns, without a general systemic effect on other molecular targets. It would be important for each oligonucleot...
Source: Frontiers in Pharmacology - April 23, 2019 Category: Drugs & Pharmacology Source Type: research

From “Serum Sickness” to “Xenosialitis”: Past, Present, and Future Significance of the Non-human Sialic Acid Neu5Gc
Conclusions and Perspectives In this review, we have discussed important milestones from the early description of “Serum-sickness” as being due to antibodies directed against Neu5Gc epitopes all the way to the present-day therapeutic implications of these antibodies in cancer therapy. Some of these milestones have been represented in a concise timeline (Figure 6). While the “Xenosialitis” hypothesis is well-supported in the human-like mouse models, it has yet to be conclusively proven in humans. It remains to be seen if “Xenosialitis” plays a role in other uniquely-human dis...
Source: Frontiers in Immunology - April 16, 2019 Category: Allergy & Immunology Source Type: research

ST18 Enhances PV-IgG-Induced Loss of Keratinocyte Cohesion in Parallel to Increased ERK Activation
Discussions Autoantibodies targeting Dsg1 and Dsg3 are pathogenic and cause blister formation by inducing structural desmosomal changes in the skin of PV patients (42). However, the mechanisms underlying disease development and the factors enhancing its manifestation have not yet been fully elucidated. Secondary factors promoting severity of the disease include non-Dsg antibodies (43) as well as genetic alterations such as recently reported ST18 SNPs (29–31) and may also entail keratinocyte-derived cytokine release. Here, we investigate the effect of ST18 overexpression and cytokine secretion on PV-IgG mediated l...
Source: Frontiers in Immunology - April 16, 2019 Category: Allergy & Immunology Source Type: research

Editorial: Shaping of Human Immune System and Metabolic Processes by Viruses and Microorganisms
Conclusions In conclusion, articles in this Research Topic made a very significant contribution to our understanding of the role played by environmental factors, dysbiotic conditions, and infections in triggering diseases. Since this is a rapidly expanding area of research, many other factors contributing to the onset of these diseases are not covered here. We are confident, however, that further studies will expand the list as well as bring a better understanding of mechanisms involved in the onset of autoimmune and autoinflammatory diseases. Author Contributions All authors listed have made a substantial, direct and i...
Source: Frontiers in Microbiology - April 16, 2019 Category: Microbiology Source Type: research

IL-33 Mediated Inflammation in Chronic Respiratory Diseases —Understanding the Role of the Member of IL-1 Superfamily
Conclusion Analysis of the pleiotropic effects of IL-33 on multiple immunological cells (macrophages, mastocytes), as well as neurological cells of medulla oblongata, dorsal root ganglion, antigen-induced arthritis system, carrageen, and formalin, shows that this alarmin plays curtail, yet not fully known role in mediating inflammation, especially in chronic inflammatory pulmonary diseases such as asthma, COPD, and OSA. Taken into consideration the engagement in this process, in particular of mastocytes and their secretion of CXCL2, 4, 8, and other cytokines, there is no doubt regarding the etiopathogenic role of IL-33 in...
Source: Frontiers in Immunology - April 15, 2019 Category: Allergy & Immunology Source Type: research

Plant-Derived Alkaloids: The Promising Disease-Modifying Agents for Inflammatory Bowel Disease
Conclusion This paper summarizes the current findings regarding the anti-colitis activity of plant-derived alkaloids and shows how these alkaloids exhibit significant and beneficial effects in alleviating colonic inflammation. These natural alkaloids are not only promising agents for IBD treatment but are also components for developing new wonder drugs. However, the underlying molecular mechanisms or toxicological evaluation of most plant-derived alkaloids still require much scientific research, and their actual efficacies for IBD patients have not been verified well in field research. Thus, further clinical trials to elu...
Source: Frontiers in Pharmacology - April 11, 2019 Category: Drugs & Pharmacology Source Type: research

The Study of Dried Ginger and Linggan Wuwei Jiangxin Decoction Treatment of Cold Asthma Rats Using GC –MS Based Metabolomics
Conclusion In this study, serum and urine metabolites identified by GC–MS and general pharmacodynamic evaluation (morphological observation, histopathology, inflammatory factors, and visceral indices) were used to compare the effects of GJ and LGWWJX decoctions on cold asthma. Significant metabolic abnormalities were observed for 37 metabolites (15 in serum, 22 in urine) in rats with cold asthma. These altered metabolites might be potential biomarkers or therapeutic targets during development of cold asthma. Furthermore, pathway analysis demonstrated that pathways associated with energy metabolism and oxidative str...
Source: Frontiers in Pharmacology - April 10, 2019 Category: Drugs & Pharmacology Source Type: research

Contribution of Non-immune Cells to Activation and Modulation of the Intestinal Inflammation
Conclusions As the intestinal mucosa surface constitutes the major surface of the body which is in direct contact with the outer environment, intestinal immune homeostasis must be accurately regulated. The interplay between commensal microbiota, intestinal stromal cells, and the mucosal immune system components should guarantee the intestinal homeostasis to avoid a sustained inflammation that could induce tissue damage. However, several factors can lead to inflammation through homeostasis breakdown. Figure 1 summarizes the main points that have been reviewed here. We have described what it is known so far about the role o...
Source: Frontiers in Immunology - April 9, 2019 Category: Allergy & Immunology Source Type: research

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