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MASP-1 Increases Endothelial Permeability
This study was carried out in accordance with the recommendations of WMA Declaration of Helsinki with written informed consent from all subjects. All subjects gave written informed consent in accordance with the Declaration of Helsinki. The protocol was approved by the Semmelweis University Institutional Review Board (permission number: TUKEB141/2015). Author Contributions MLD designed and performed experiments, analyzed data, and wrote the manuscript. ZN performed the bioinformatics analysis. EK, ES, and VM contributed to cellular experiments and data analysis and commented on the manuscript. FW performed the xCELLigenc...
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

Human Gut-Associated Natural Killer Cells in Health and Disease
Alessandro Poggi1*, Roberto Benelli2, Roberta Venè1, Delfina Costa1, Nicoletta Ferrari1, Francesca Tosetti1 and Maria Raffaella Zocchi3 1Molecular Oncology and Angiogenesis Unit, IRCCS Ospedale Policlinico San Martino, Genoa, Italy 2Immunology Unit, IRCCS Ospedale Policlinico San Martino, Genoa, Italy 3Division of Immunology, Transplantation and Infectious Diseases, IRCCS San Raffaele Scientific Institute, Milan, Italy It is well established that natural killer (NK) cells are involved in both innate and adaptive immunity. Indeed, they can recognize molecules induced at the cell surface by stress signals...
Source: Frontiers in Immunology - May 2, 2019 Category: Allergy & Immunology Source Type: research

Loss-of-Function in SMAD4 Might Not Be Critical for Human Natural Killer Cell Responsiveness to TGF- β
This study was carried out in accordance with approval of the Melbourne Health and Walter and Eliza Hall Institute of Medical Research's Human Research Ethics Committee (approval number: 2013.081). All subjects gave written informed consent for participation and publication. Results and Discussion TGF-β signaling in NK cells is associated with: phosphorylation in SMAD2 and 3, inhibition of IL-15-induced metabolism/proliferation, simultaneous downregulation of CD44, CD49e, and Eomes, and upregulation of CD16 and CD49a expression (7, 10). SMAD family member 4 (SMAD4) belongs to the SMAD family of transcript...
Source: Frontiers in Immunology - April 30, 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

Hepatic Natural Killer Cells: Organ-Specific Sentinels of Liver Immune Homeostasis and Physiopathology
Joanna Mikulak1,2, Elena Bruni1,2, Ferdinando Oriolo1,2, Clara Di Vito1 and Domenico Mavilio1,2* 1Unit of Clinical and Experimental Immunology, Humanitas Clinical and Research Center, Milan, Italy 2Department of Medical Biotechnologies and Translational Medicine, University of Milan, Milan, Italy The liver is considered a preferential tissue for NK cells residency. In humans, almost 50% of all intrahepatic lymphocytes are NK cells that are strongly imprinted in a liver-specific manner and show a broad spectrum of cellular heterogeneity. Hepatic NK (he-NK) cells play key roles in tuning liver immune response in b...
Source: Frontiers in Immunology - April 29, 2019 Category: Allergy & Immunology Source Type: research

Functional Antibody Responses Following Allogeneic Stem Cell Transplantation for TP53 Mutant pre-B-ALL in a Patient With X-Linked Agammaglobulinemia
Discussion This case demonstrates successful cure of pre-B-ALL complicating XLA by alloSCT with restoration of B-cell development and functional antibody response. We are aware of only one previous case of pre-B-ALL in an XLA patient (21), which suggests that human BTK deficiency in itself does not predispose to pre-B-ALL. However, there are data to suggest that BTK may act as a tumor suppressor, and BTK deficiency may predispose to tumor development following a “second hit.” Mice with a genetic deficiency in Slp65, a gene encoding an adaptor protein that functions together with BTK, have a block in proge...
Source: Frontiers in Immunology - April 25, 2019 Category: Allergy & Immunology 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

Th2-TRMs Maintain Life-Long Allergic Memory in Experimental Asthma in Mice
This study was carried out in strict accordance with the guidelines for the care and use of laboratory animals of the Austrian Ministry of Science. The protocol was approved by the Committee on the Ethics of the Austrian Ministry of Science (Number: GZ: 66.009/0330-II/3b/2013). All painful procedures were performed under anesthesia, and all efforts were made to minimize suffering. Author Contributions BB designed and performed experiments, analyzed the samples and contributed to the manuscript preparation. SK designed and performed experiments, analyzed the samples and contributed to the manuscript preparation. LA perfor...
Source: Frontiers in Immunology - April 23, 2019 Category: Allergy & Immunology Source Type: research

Scurfy Mice Develop Features of Connective Tissue Disease Overlap Syndrome and Mixed Connective Tissue Disease in the Absence of Regulatory T Cells
Discussion Treg represent a lineage of T cells which play a fundamental role in maintaining humoral tolerance in the periphery. This subset of “suppressor T cells” is identified as FoxP3-expressing CD4+ T cells (16, 17). The unrestrained expression of FoxP3 is essential for the development and function of Treg (4). Accordingly, a disruption of the Foxp3 gene in scurfy mice results in an autoimmune lymphoproliferative disorder with fatal multi-organ inflammation (18). Since the causative mutation occurs in orthologous genes, the scurfy phenotype is indicated as the murine equivalent of the human IPEX sy...
Source: Frontiers in Immunology - April 23, 2019 Category: Allergy & Immunology Source Type: research

The Emerging Epigenetic Role of CD8+T Cells in Autoimmune Diseases: A Systematic Review
The Emerging Epigenetic Role of CD8+T Cells in Autoimmune Diseases: A Systematic Review Qiancheng Deng1, Yangyang Luo1,2, Christopher Chang3, Haijing Wu1, Yan Ding4* and Rong Xiao1* 1Hunan Key Laboratory of Medical Epigenetics, Department of Dermatology, The Second Xiangya Hospital, Central South University, Changsha, China 2Department of Dermatology, Hunan Children's Hospital, Changsha, China 3Division of Rheumatology, Allergy and Clinical Immunology, University of California, Davis, Davis, CA, United States 4Department of Dermatology, Hainan Provincial Dermatology Disease Hospital, Haikou, China A...
Source: Frontiers in Immunology - April 17, 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

Group 2 Innate Lymphoid Cells Are Redundant in Experimental Renal Ischemia-Reperfusion Injury
In this study, we sought to further characterize ILC2s in the kidney, their location within this organ and determine their functional role in IRI using a loss-of-function approach. Here, we found that kidney ILC2s constitutively express IL-5 and are primarily located in close proximity to the renal vasculature, within the adventitia. Additionally, we demonstrate that a reduction, deficiency or depletion of ILC2s had minimal impact on the severity of IRI. Whilst activation of ILC2s and the associated amplification of local type 2 immunity has been previously shown to reduce the deleterious consequences of AKI, our results r...
Source: Frontiers in Immunology - April 15, 2019 Category: Allergy & Immunology Source Type: research

Cellular Immune Function in Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS)
This study was carried out in accordance with the recommendations of The London School of Hygiene & Tropical Medicine (LSHTM) Research Ethics Committee (Ref. 6123) and the National Research Ethics Service (NRES) London-Bloomsbury Research Ethics Committee (REC ref. 11/10/1760, IRAS ID: 77765), with written informed consent from all subjects. All subjects gave written informed consent in accordance with the Declaration of Helsinki. The protocol was approved by the LSHTM Research Ethics Committee and the NRES London-Bloomsbury Research Ethics Committee. Author Contributions JC, HD, LN, EL, and ER devised the study ...
Source: Frontiers in Immunology - April 15, 2019 Category: Allergy & Immunology Source Type: research

Autophagy Limits Inflammasome During Chlamydia pneumoniae Infection
In this study we found blocking autophagy led to increased CP growth in both macrophages and mouse embryonic fibroblasts. In vivo, loss of the autophagy elongation component ATG16L1 specifically in myeloid cells led to increased mortality in response to CP infection, characterized by greater numbers of neutrophils and dendritic cells, but no change in the CP burden in the lungs. This was accompanied by an increase in inflammasome-active macrophages and IL-1β production. While induction of autophagy in macrophages led to reduced CP growth in vitro, in vivo treatment with rapamycin led to increased mortality of infec...
Source: Frontiers in Immunology - April 11, 2019 Category: Allergy & Immunology Source Type: research

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