Therapeutic Approaches Targeting the Natural Killer-Myeloid Cell Axis in the Tumor Microenvironment
Immunotherapy has transformed cancer treatment by promoting durable clinical responses in a proportion of patients; however, treatment still fails in many patients. Innate immune cells play a key role in the response to immunotherapy. Crosstalk between innate and adaptive immune systems drives T-cell activation but also limits immunotherapy response, as myeloid cells are commonly associated with resistance. Hence, innate cells have both negative and positive effects within the tumor microenvironment (TME), and despite investment in early clinical trials targeting innate cells, they have seen limited success. Suppressive my...
Source: Frontiers in Immunology - April 19, 2021 Category: Allergy & Immunology Source Type: research

Lung Marginated and Splenic Murine Resident Neutrophils Constitute Pioneers in Tissue-Defense During Systemic E. coli Challenge
The rapid response of neutrophils throughout the body to a systemic challenge is a critical first step in resolution of bacterial infection such as Escherichia coli (E. coli). Here we delineated the dynamics of this response, revealing novel insights into the molecular mechanisms using lung and spleen intravital microscopy and 3D ex vivo culture of living precision cut splenic slices in combination with fluorescent labelling of endogenous leukocytes. Within seconds after challenge, intravascular marginated neutrophils and lung endothelial cells (ECs) work cooperatively to capture pathogens. Neutrophils retained on lung ECs...
Source: Frontiers in Immunology - April 19, 2021 Category: Allergy & Immunology Source Type: research

Infection Temperature Affects the Phenotype and Function of Chimeric Antigen Receptor T Cells Produced via Lentiviral Technology
This study reported for the first time the influence of differences in infection temperature on the phenotype and function of produced CAR-T cells. Our results show that infection at 4 degrees produces the highest CAR-positive rate of T cells, infection at 37 degrees produces the fastest proliferation in CAR-T cells, and infection at 32 degrees produces CAR-T cells with the greatest proportion of naive cells and the lowest expression of immune checkpoints. Therefore, infection at 32 degrees is recommended to prepare CAR-T cells. CAR-T cells derived from infection at 32 degrees seem to have a balance between function and ph...
Source: Frontiers in Immunology - April 19, 2021 Category: Allergy & Immunology Source Type: research

Oxidative Stress-Mediated YAP Dysregulation Contributes to the Pathogenesis of Pemphigus Vulgaris
In conclusion, this study suggests that oxidative stress coupled with YAP dysregulation attributes to PV blistering, implying antioxidants may be beneficial in the treatment of PV. (Source: Frontiers in Immunology)
Source: Frontiers in Immunology - April 19, 2021 Category: Allergy & Immunology Source Type: research

Neoepitopes in Type 1 Diabetes: Etiological Insights, Biomarkers and Therapeutic Targets
The mechanisms underlying type 1 diabetes (T1D) pathogenesis remain largely unknown. While autoantibodies to pancreatic beta-cell antigens are often the first biological response and thereby a useful biomarker for identifying individuals in early stages of T1D, their role in T1D pathogenesis is not well understood. Recognition of these antigenic targets by autoreactive T-cells plays a pathological role in T1D development. Recently, several beta-cell neoantigens have been described, indicating that both neoantigens and known T1D antigens escape central or peripheral tolerance. Several questions regarding the mechanisms by w...
Source: Frontiers in Immunology - April 19, 2021 Category: Allergy & Immunology Source Type: research

Predictive Value of KDM5C Alterations for Immune Checkpoint Inhibitors Treatment Outcomes in Patients With Cancer
Lysine (K)-specific demethylase 5C (KDM5C) plays a significant role in the tumor cell proliferation, invasion, drug resistance and the regulation of tumor-related gene expression. Here, we aimed to investigate its predictive value in patients with cancers received immune checkpoint inhibitors (ICIs). We explored the predictive value of KDM5C alterations and the association between KDM5C alteration and immune landscape by using published cohort with clinical outcome and sequenced data from online database. The frequency of KDM5C alterations was 2.1% across 48045 tumor samples with different cancers from 185 studies. KDM5C a...
Source: Frontiers in Immunology - April 19, 2021 Category: Allergy & Immunology Source Type: research

The Architecture of Circulating Immune Cells Is Dysregulated in People Living With HIV on Long Term Antiretroviral Treatment and Relates With Markers of the HIV-1 Reservoir, Cytomegalovirus, and Microbial Translocation
In conclusion, this comprehensive analysis confirms the importance of persistent abnormalities in the number and function of circulating immune cells in PLHIV on stable treatment. (Source: Frontiers in Immunology)
Source: Frontiers in Immunology - April 19, 2021 Category: Allergy & Immunology Source Type: research

Host-Directed Therapies: Modulating Inflammation to Treat Tuberculosis
Following infection with Mycobacterium tuberculosis, the causative agent of tuberculosis (TB), most human hosts are able to contain the infection and avoid progression to active TB disease through expression of a balanced, homeostatic immune response. Proinflammatory mechanisms aiming to kill, slow and sequester the pathogen are key to a successful host response. However, an excessive or inappropriate pro-inflammatory response may lead to granuloma enlargement and tissue damage, which may prolong the TB treatment duration and permanently diminish the lung function of TB survivors. The host also expresses certain anti-infla...
Source: Frontiers in Immunology - April 19, 2021 Category: Allergy & Immunology Source Type: research

Molecular Characterization of Complement Component 3 (C3) in the Pearl Oyster Pinctada fucata Improves Our Understanding of the Primitive Complement System in Bivalve
As the central component in the complement system, complement component 3 (C3) plays essential roles in both the innate and adaptive immune responses. Here, a C3 gene (designated as pf-C3) was obtained from the pearl oyster Pinctada fucata by RT-PCR and rapid amplification of cDNA ends (RACE). The pf-C3 cDNA consists of 5,634 bp with an open reading frame (ORF) of 5,193 bp encoding a protein of 1,730 amino acids with a 19 residue signal peptide. The deduced pf-C3 protein possessed the characteristic structural features present in its homologs and contained the A2M_N_2, ANATO, A2M, A2M_comp, A2M_recep, and C345C domains, as...
Source: Frontiers in Immunology - April 19, 2021 Category: Allergy & Immunology Source Type: research

Glycolytic Metabolism Is Critical for the Innate Antibacterial Defense in Acute Streptococcus pneumoniae Otitis Media
ConclusionS.pn infection induced increased glycolysis conversion during AOM, which promoted inflammatory responses and bacterial clearance, but also aggravated tissue damage. (Source: Frontiers in Immunology)
Source: Frontiers in Immunology - April 19, 2021 Category: Allergy & Immunology Source Type: research

Lymphocyte Non-Specific Function Detection Facilitating the Stratification of Mycobacterium tuberculosis Infection
ConclusionsLymphocyte non-specific function detection offers an attractive alternative to facilitate TB diagnosis. The three-index diagnostic model was proved to be a potent tool for the identification of different events involved in TB infection, which is helpful for the treatment and management of patients. (Source: Frontiers in Immunology)
Source: Frontiers in Immunology - April 19, 2021 Category: Allergy & Immunology Source Type: research

pH-Controlled Release of Antigens Using Mesoporous Silica Nanoparticles Delivery System for Developing a Fish Oral Vaccine
In this study, dihydrolipoamide dehydrogenase (DLDH) antigens of Vibrio alginolyticus were loaded into mesoporous silica nanoparticles (MSN) to compose the vaccine delivery system. Hydroxypropyl methylcellulose phthalate (HP55) was coated to provide protection of immunogen. The morphology, loading capacity, acid-base triggered release were characterized and the toxicity of nanoparticle vaccine was determined in vitro. Further, the vaccine immune effects were evaluated in large yellow croaker via oral administration. In vitro studies confirmed that the antigen could be stable in enzymes-rich artificial gastric fluid and rel...
Source: Frontiers in Immunology - April 19, 2021 Category: Allergy & Immunology Source Type: research

LUBAC Suppresses IL-21-Induced Apoptosis in CD40-Activated Murine B Cells and Promotes Germinal Center B Cell Survival and the T-Dependent Antibody Response
B cell activation by Tfh cells, i.e., through CD154 engagement of CD40 and IL-21, and survival within GCs are crucial for the T-dependent Ab response. LUBAC, composed of HOIP, SHARPIN, and HOIL-1, catalyzes linear ubiquitination (Linear M1-Ub) to mediate NF-κB activation and cell survival induced by TNF receptor superfamily members, which include CD40. As shown in this study, B cells expressing the Sharpin null mutation cpdm (Sharpincpdm) could undergo proliferation, CSR, and SHM in response to immunization by a T-dependent Ag, but were defective in survival within GCs, enrichment of a mutation enhancing the BCR affi...
Source: Frontiers in Immunology - April 19, 2021 Category: Allergy & Immunology Source Type: research

Targeting Enclysis in Liver Autoimmunity, Transplantation, Viral Infection and Cancer
We describe enclysis as is a natural process of liver immune regulation that lends itself to therapeutic targeting, particularly in combination with current Treg cell approaches. (Source: Frontiers in Immunology)
Source: Frontiers in Immunology - April 19, 2021 Category: Allergy & Immunology Source Type: research

Modular Organization of Engulfment Receptors and Proximal Signaling Networks: Avenues to Reprogram Phagocytosis
Transmembrane protein engulfment receptors expressed on the surface of phagocytes engage ligands on apoptotic cells and debris to initiate a sequence of events culminating in material internalization and immunologically beneficial outcomes. Engulfment receptors are modular, comprised of functionally independent extracellular ligation domains and cytosolic signaling motifs. Cognate kinases, adaptors, and phosphatases regulate engulfment by controlling the degree of receptor activation in phagocyte plasma membranes, thus acting as receptor-proximal signaling modules. Here, we review recent efforts to reprogram phagocytes usi...
Source: Frontiers in Immunology - April 19, 2021 Category: Allergy & Immunology Source Type: research

Co-Isolation of Cytokines and Exosomes: Implications for Immunomodulation Studies
Exosomes play a vital role in intercellular communication and their immunomodulatory potential have become an important focus in cancer research. Various methods have been developed for the isolation although each method differs in the number and purity of exosomes they yield. In melanoma, tumor-derived exosomes drive immunosuppression within the tumor microenvironment. The co-elution of exosomes and soluble factors such as cytokines during isolation, however, make it difficult to ascertain the contribution of exosome cargo, as soluble cytokines are equally capable of immune suppression. In this review we will expound upon...
Source: Frontiers in Immunology - April 19, 2021 Category: Allergy & Immunology Source Type: research

Neuro-Immune Cross-Talk in the Striatum: From Basal Ganglia Physiology to Circuit Dysfunction
The basal ganglia network is represented by an interconnected group of subcortical nuclei traditionally thought to play a crucial role in motor learning and movement execution. During the last decades, knowledge about basal ganglia physiology significantly evolved and this network is now considered as a key regulator of important cognitive and emotional processes. Accordingly, the disruption of basal ganglia network dynamics represents a crucial pathogenic factor in many neurological and psychiatric disorders. The striatum is the input station of the circuit. Thanks to the synaptic properties of striatal medium spiny neuro...
Source: Frontiers in Immunology - April 19, 2021 Category: Allergy & Immunology Source Type: research

Development of Stable Chimeric IL-15 for Trans-Presentation by the Antigen Presenting Cells
IL-15 is one of the important biologics considered for vaccine adjuvant and treatment of cancer. However, a short half-life and poor bioavailability limit its therapeutic potential. Herein, we have structured IL-15 into a chimeric protein to improve its half-life enabling greater bioavailability for longer periods. We have covalently linked IL-15 with IgG2 base to make the IL-15 a stable chimeric protein, which also increased its serum half-life by 40 fold. The dimeric structure of this kind of IgG based biologics has greater stability, resistance to proteolytic cleavage, and less frequent dosing schedule with minimum dosa...
Source: Frontiers in Immunology - April 19, 2021 Category: Allergy & Immunology Source Type: research

Tregitopes Improve Asthma by Promoting Highly Suppressive and Antigen-Specific Tregs
Tregitopes (T regulatory epitopes) are IgG-derived peptides with high affinity to major histocompatibility complex class II (MHCII), that are known to promote tolerance by activating T regulatory cell (Treg) activity. Here we characterized the effect of IgG Tregitopes in a well-established murine model of allergic asthma, demonstrating in vivo antigen-specific tolerance via adoptive transfer of Tregitope-and-allergen-activated Tregs. Asthma is a heterogeneous chronic inflammatory condition affecting the airways and impacting over 300 million individuals worldwide. Treatment is suppressive, and no current therapy addresses ...
Source: Frontiers in Immunology - April 19, 2021 Category: Allergy & Immunology Source Type: research

A Comparison Between Recombinant Listeria GAPDH Proteins and GAPDH Encoding mRNA Conjugated to Lipids as Cross-Reactive Vaccines for Listeria, Mycobacterium, and Streptococcus
Cross-reactive vaccines recognize common molecular patterns in pathogens and are able to confer broad spectrum protection against different infections. Antigens common to pathogenic bacteria that induce broad immune responses, such as the glyceraldehyde-3-phosphate dehydrogenase (GAPDH) of the genera Listeria, Mycobacterium, or Streptococcus, whose sequences present more than 95% homology at the N-terminal GAPDH1−22 peptide, are putative candidates for universal vaccines. Here, we explore vaccine formulations based on dendritic cells (DC) loaded with two molecular forms of Listeria monocytogenes GAPDH (LM-GAPDH), suc...
Source: Frontiers in Immunology - April 19, 2021 Category: Allergy & Immunology Source Type: research

High Dimensional Imaging Mass Cytometry Panel to Visualize the Tumor Immune Microenvironment Contexture
We describe here the design of a 39-antibody IMC panel for the staining of formalin-fixed paraffin-embedded human tumor sections. We also provide an optimized staining procedure and details of the experimental workflow. This panel deciphers the nature of immune cells, their functions and their interactions with tumor cells and cancer-associated fibroblasts as well as with other TiME structural components known to be associated with tumor progression like nerve fibers and tumor extracellular matrix proteins. This panel represents a valuable innovative and powerful tool for fundamental and clinical studies that could be used...
Source: Frontiers in Immunology - April 16, 2021 Category: Allergy & Immunology Source Type: research

Bile Acids Impair Vaccine Response in Children With Biliary Atresia
ConclusionThis study reveals the overall vaccination rates of routine vaccines in Chinese BA children are very low and the poor HBV vaccine responses are associated with bile acids, possibly via the inhibition of CD19+CD27+IgG+ post-class-switched memory B cell response.Clinical Trial Registrationhttp://www.chictr.org.cn, identifier ChiCTR1800019165. (Source: Frontiers in Immunology)
Source: Frontiers in Immunology - April 16, 2021 Category: Allergy & Immunology Source Type: research

Adapting T Cell Receptor Ligand Discrimination Capability via LAT
Self- and non-self ligand discrimination is a core principle underlying T cell-mediated immunity. Mature αβ T cells can respond to a foreign peptide ligand presented by major histocompatibility complex molecules (pMHCs) on antigen presenting cells, on a background of continuously sensed self–pMHCs. How αβ T cells can properly balance high sensitivity and high specificity to foreign pMHCs, while surrounded by a sea of self-peptide ligands is not well understood. Such discrimination cannot be explained solely by the affinity parameters of T cell antigen receptor (TCR) and pMHC interaction. In this...
Source: Frontiers in Immunology - April 16, 2021 Category: Allergy & Immunology Source Type: research

PRAK Promotes the Pathogen Clearance by Macrophage Through Regulating Autophagy and Inflammasome Activation
The p38 regulated/activated protein kinase (PRAK) is a protein kinase downstream of p38MAPK. The present study investigated its function in the macrophage. Myeloid-specific deletion of Prak resulted in a significant reduction in F4/80+CD11b+ peritoneal macrophages with decreased expression of MHC-II and CD80. Upon infection with Listeria monocytogenes, Prak-deficient mice demonstrated an increased mortality, which was accompanied by a higher bacterial load in multiple tissues and elevated levels of proinflammatory cytokines in the serum. While the Prak-deficient macrophage showed similar potency in phagocytosis assays, its...
Source: Frontiers in Immunology - April 16, 2021 Category: Allergy & Immunology Source Type: research

COVID-19 Among Patients With Inflammatory Rheumatic Diseases
ConclusionsAmong IRD patients with COVID-19, comorbidities and glucocorticoid use were associated with a worse outcome, while biologic DMARDs do not seem to be associated with a worse outcome. (Source: Frontiers in Immunology)
Source: Frontiers in Immunology - April 16, 2021 Category: Allergy & Immunology Source Type: research

Designing Multi-Antigen Vaccines Against Acinetobacter baumannii Using Systemic Approaches
This study supports the idea that integration of multi-omic data and fundamental knowledge of the pathobiology of drug-resistant bacteria can facilitate the development of effective multi-antigen vaccines against these challenging infections. (Source: Frontiers in Immunology)
Source: Frontiers in Immunology - April 16, 2021 Category: Allergy & Immunology Source Type: research

Novel Biomarkers of Dynamic Blood PD-L1 Expression for Immune Checkpoint Inhibitors in Advanced Non-Small-Cell Lung Cancer Patients
ConclusionThere was a positive correlation between bPD-L1 and tPD-L1 expression. Increased expression of PD-L1 mRNA, exoPD-L1, or both in early stage of ICIs treatment could serve as positive biomarkers of efficacy and OS in advanced NSCLC patients. (Source: Frontiers in Immunology)
Source: Frontiers in Immunology - April 16, 2021 Category: Allergy & Immunology Source Type: research

SLAM Associated Protein Signaling in T Cells: Tilting the Balance Toward Autoimmunity
T cell activation is the result of the integration of signals across the T cell receptor and adjacent co-receptors. The signaling lymphocyte activation molecules (SLAM) family are transmembrane co-receptors that modulate antigen driven T cell responses. Signal transduction downstream of the SLAM receptor is mediated by the adaptor protein SLAM Associated Protein (SAP), a small intracellular protein with a single SH2 binding domain that can recruit tyrosine kinases as well as shield phosphorylated sites from dephosphorylation. Balanced SLAM-SAP signaling within T cells is required for healthy immunity, with deficiency or ov...
Source: Frontiers in Immunology - April 16, 2021 Category: Allergy & Immunology Source Type: research

Role of Circulating T Follicular Helper Cells and Stem-Like Memory CD4+ T Cells in the Pathogenesis of HIV-2 Infection and Disease Progression
CD4+ T cells are critical players in the host adaptive immune response. Emerging evidence suggests that certain CD4+ T cell subsets contribute significantly to the production of neutralizing antibodies and help in the control of virus replication. Circulating T follicular helper cells (Tfh) constitute a key T cell subset that triggers the adaptive immune response and stimulates the production of neutralizing antibodies (NAbs). T cells having stem cell-like property, called stem-like memory T cells (Tscm), constitute another important subset of T cells that play a critical role in slowing the rate of disease progression thr...
Source: Frontiers in Immunology - April 16, 2021 Category: Allergy & Immunology Source Type: research

Likelihood Ratio Approach and Clinical Interpretation of Laboratory Tests
(Source: Frontiers in Immunology)
Source: Frontiers in Immunology - April 16, 2021 Category: Allergy & Immunology Source Type: research

Listening to the Whispers in Neuroimmune Crosstalk: A Comprehensive Workflow to Investigate Neurotrophin Receptor p75NTR Under Endogenous, Low Abundance Conditions
Inflammatory conditions are critically influenced by neuroimmune crosstalk. Cytokines and neurotrophic factors shape the responses of both nervous and immune systems. Although much progress has been made, most findings to date are based on expression of recombinant (tagged) proteins. The examination of receptor interactions by immunoprecipitation (IP) at endogenous levels provides further insight into the more subtle regulations of immune responses. Here, we present a comprehensive workflow and an optimized IP protocol that provide step-by-step instructions to investigate neurotrophin receptor p75NTR at endogenous, low abu...
Source: Frontiers in Immunology - April 16, 2021 Category: Allergy & Immunology Source Type: research

Discovery and Validation of a Three-Cytokine Plasma Signature as a Biomarker for Diagnosis of Pediatric Tuberculosis
Pediatric TB poses challenge in diagnosis due to the paucibacillary nature of the disease. We conducted a prospective diagnostic study to identify immune biomarkers of pediatric TB and controls (discovery cohort) and obtained a separate “validation” cohort of confirmed cases of pediatric TB and controls. Multiplex ELISA was performed to examine the plasma levels of cytokines. Discovery and validation cohorts revealed that baseline plasma levels of IFNγ, TNFα, IL-2, and IL-17A were significantly higher in active TB (confirmed TB and unconfirmed TB) in comparison to unlikely TB children. Receiver oper...
Source: Frontiers in Immunology - April 16, 2021 Category: Allergy & Immunology Source Type: research

The Predictive Value of Monocytes in Immune Microenvironment and Prognosis of Glioma Patients Based on Machine Learning
Gliomas are primary malignant brain tumors. Monocytes have been proved to actively participate in tumor growth. Weighted gene co-expression network analysis was used to identify meaningful monocyte-related genes for clustering. Neural network and SVM were applied for validating clustering results. Somatic mutation and copy number variation were used for defining the features of identified clusters. Differentially expressed genes (DEGs) between the stratified groups after performing elastic regression and principal component analyses were used for the construction of risk scores. Monocytes were associated with glioma patien...
Source: Frontiers in Immunology - April 16, 2021 Category: Allergy & Immunology Source Type: research

A Partial Picture of the Single-Cell Transcriptomics of Human IgA Nephropathy
We presented a comprehensive scRNA-seq analysis of human renal biopsies from IgAN. We showed for the first time that IgAN mesangial cells displayed increased expression of several novel genes including MALAT1, GADD45B, SOX4, and EDIL3, which were related to cell proliferation and matrix accumulation. The overexpressed genes in tubule cells of IgAN were mainly enriched in inflammatory pathways including TNF signaling, IL-17 signaling, and NOD-like receptor signaling. Furthermore, we compared the results of 4 IgAN patients with the published scRNA-Seq data of healthy kidney tissues of three human donors in order to further v...
Source: Frontiers in Immunology - April 16, 2021 Category: Allergy & Immunology Source Type: research

SAMD9 Is Relating With M2 Macrophage and Remarkable Malignancy Characters in Low-Grade Glioma
Immunoreactions regulated by TAMs (Tumor-associated macrophages) play a pivotal role in tumorigenesis and metastasis. In recent decades, treatments based on immune regulation have achieved revolutionary breakthroughs in cancer targeted therapies. The phenotypes of TAMs in gliomas are more heterogeneous and inherently complex than can be simply defined by classification into the M1 and M2 polarized states. The detailed mechanisms surrounding infiltrating macrophage phenotype and glioma characteristics remain undefined. SAMD9 (Sterile Alpha Motif Domain-Containing Protein 9) was found to be highly expressed in glioma and clo...
Source: Frontiers in Immunology - April 16, 2021 Category: Allergy & Immunology Source Type: research

Wiskott Aldrich Syndrome: A Multi-Institutional Experience From India
ConclusionsWe report the first nationwide cohort of patients with WAS from India. Bleeding episodes and infections are common manifestations. Mortality continues to be high as curative therapy is not accessible to most of our patients. (Source: Frontiers in Immunology)
Source: Frontiers in Immunology - April 16, 2021 Category: Allergy & Immunology Source Type: research

Revisit of Optimal Donor Number Estimation in the Hong Kong Bone Marrow Donor Registry
High resolution typing of the HLA-DPB1 locus for patient who requested for hematopoietic stem cell transplantation (HSCT) workup has recently become mandatory by the National Marrow Donor Program (NMDP) in order to facilitate matching between donors and recipients for better outcomes. The likelihood of identifying HLA matched donors in Hong Kong, on top of the existing HLA-A, -B, -C, and -DRB1 loci, is revisited in this study. HLA-A, -B, -C, -DRB1 and -DPB1 genotypes of 5,266 volunteer unrelated Chinese donors from the Hong Kong Bone Marrow Donor Registry (HKBMDR), were included in this study. Matching models were employed...
Source: Frontiers in Immunology - April 16, 2021 Category: Allergy & Immunology Source Type: research

Genome-Wide Gene Expression Analysis of Mtb-Infected DC Highlights the Rapamycin-Driven Modulation of Regulatory Cytokines via the mTOR/GSK-3 β Axis
In conclusion, our study sheds light on the molecular mechanism by which autophagy induction contributes to DC activation during Mtb infection and points to rapamycin and GSK-3β modulators as promising compounds for host-directed therapy in the control of Mtb infection. (Source: Frontiers in Immunology)
Source: Frontiers in Immunology - April 16, 2021 Category: Allergy & Immunology Source Type: research

Opportunities and Challenges in Democratizing Immunology Datasets
We present use cases for repurposing open-access immunology datasets with advanced machine learning applications and more. (Source: Frontiers in Immunology)
Source: Frontiers in Immunology - April 16, 2021 Category: Allergy & Immunology Source Type: research

Establishing a Risk Prediction Model for Atherosclerosis in Systemic Lupus Erythematosus
Conclusions: We built an atherosclerotic risk prediction model with one gene and two clinical factors. This model may greatly assist clinicians to identify SLE patients with atherosclerosis, especially asymptomatic atherosclerosis. (Source: Frontiers in Immunology)
Source: Frontiers in Immunology - April 16, 2021 Category: Allergy & Immunology Source Type: research

Case Report: Splenic Irradiation for the Treatment of Chronic Active Antibody-Mediated Rejection in Kidney Allograft Recipients With De Novo Donor-Specific Antibodies
Chronic active antibody-mediated rejection (AMR) in renal transplantation is usually refractory to current conventional treatment with rituximab, plasmapheresis (PP), and intravenous immunoglobulins (IVIG). Splenic irradiation has been reported to be effective in the rescue of early severe acute AMR after kidney transplantation; however, its effect in chronic active AMR has not been reported to date. In order to reduce donor-specific antibody (DSA) and prevent the progression of chronic AMR, we used repetitive low-dose splenic irradiation, together with rituximab and PP/IVIG, in two living-related kidney transplant recipie...
Source: Frontiers in Immunology - April 15, 2021 Category: Allergy & Immunology Source Type: research

Immune-Therapy-Related Toxicity Events and Dramatic Remission After a Single Dose of Pembrolizumab Treatment in Metastatic Thymoma: A Case Report
In conclusion, the clinical utilization of immunotherapy is an encouraging therapeutic alternative for advanced thymomas. At the same time, patients have to be monitored very carefully, because of the risk to develop irAEs. (Source: Frontiers in Immunology)
Source: Frontiers in Immunology - April 15, 2021 Category: Allergy & Immunology Source Type: research

Lipoxin A4 Restores Septic Renal Function via Blocking Crosstalk Between Inflammation and Premature Senescence
In this study, rats developed AKI following cecal ligation and puncture (CLP), as evidenced by a dynamic increase in serum creatinine, blood urea nitrogen, urinary kidney injury molecule-1, neutrophil gelatinase-associated lipocalin, and pathological injury, accompanied by increased levels of inflammation (IL-6, TNF-α, and HMGB1) and tubular cell senescence. While, on the one hand, inhibition of senescence with rapamycin restored renal function and attenuated septic inflammatory response, on the other hand, LXA4 administration inhibited renal inflammation and tubular epithelial cell senescence after CLP. Ultimately, ...
Source: Frontiers in Immunology - April 15, 2021 Category: Allergy & Immunology Source Type: research

Circulating Interleukins and Risk of Multiple Sclerosis: A Mendelian Randomization Study
In this study, we applied Mendelian randomization (MR) approaches to address the causal associations between genetically determined circulating levels of ILs and the risk of MS.MethodsGenetic instruments for circulating IL-1 receptor antagonist (IL-1Ra), IL-2 receptor α subunit (IL-2Rα), IL-6, IL-16, IL-17, and IL-18 were obtained from recently published genome-wide association studies (GWAS). Summary-level data for MS were obtained from the International Multiple Sclerosis Genetics Consortium. MR analyses were performed using the R software (version 3.6.1, The R Foundation) and the TwoSampleMR package.ResultsG...
Source: Frontiers in Immunology - April 15, 2021 Category: Allergy & Immunology Source Type: research

The Sez6 Family Inhibits Complement by Facilitating Factor I Cleavage of C3b and Accelerating the Decay of C3 Convertases
The Sez6 family consists of Sez6, Sez6L, and Sez6L2. Its members are expressed throughout the brain and have been shown to influence synapse numbers and dendritic morphology. They are also linked to various neurological and psychiatric disorders. All Sez6 family members contain 2-3 CUB domains and 5 complement control protein (CCP) domains, suggesting that they may be involved in complement regulation. We show that Sez6 family members inhibit C3b/iC3b opsonization by the classical and alternative pathways with varying degrees of efficacy. For the classical pathway, Sez6 is a strong inhibitor, Sez6L2 is a moderate inhibitor...
Source: Frontiers in Immunology - April 15, 2021 Category: Allergy & Immunology Source Type: research

CMV Status Drives Distinct Trajectories of CD4+ T Cell Differentiation
Cytomegalovirus (CMV) is one of the most commonly recognized opportunistic pathogens and remains the most influential known parameter in shaping an individual’s immune system. As such, T cells induced by CMV infection could have a long-term impact on subsequent immune responses. Accumulating evidence indicates that memory T cells developed during past bacterial and viral infection can cross-react with unrelated pathogens, including transplant antigens, and can alter responses to de novo infections, vaccines, cancers, or rejection. Therefore, careful examination of T cell responses elicited by CMV is warranted to unde...
Source: Frontiers in Immunology - April 15, 2021 Category: Allergy & Immunology Source Type: research

Age-Related Differences in Molecular Profiles for Immune Checkpoint Blockade Therapy
Immune checkpoint blockade (ICB) therapies have significantly improved the prognosis and shown considerable promise for cancer therapy; however, differences in ICB treatment efficacy between the elderly and young are unknown. We analyzed the studies enrolled in the meta-analysis using the deft approach, and found no difference in efficacy except melanoma patients receiving anti–PD-1 therapy. Similarly, higher treatment response rate and more favorable prognosis were observed in elderly patients in some cancer types (e.g., melanoma) with data from published ICB treatment clinical trials. In addition, we comprehensivel...
Source: Frontiers in Immunology - April 15, 2021 Category: Allergy & Immunology Source Type: research

C5a-C5aR1 Axis Activation Drives Envenomation Immunopathology by the Snake Naja annulifera
Systemic complement activation drives a plethora of pathological conditions, but its role in snake envenoming remains obscure. Here, we explored complement’s contribution to the physiopathogenesis of Naja annulifera envenomation. We found that N. annulifera venom promoted the generation of C3a, C4a, C5a, and the soluble Terminal Complement Complex (sTCC) mediated by the action of snake venom metalloproteinases. N. annulifera venom also induced the release of lipid mediators and chemokines in a human whole-blood model. This release was complement-mediated, since C3/C3b and C5a Receptor 1 (C5aR1) inhibition mitigated t...
Source: Frontiers in Immunology - April 15, 2021 Category: Allergy & Immunology Source Type: research

Advances of Regulatory B Cells in Autoimmune Diseases
With the ability to induce T cell activation and elicit humoral responses, B cells are generally considered as effectors of the immune system. However, the emergence of regulatory B cells (Bregs) has given new insight into the role of B cells in immune responses. Bregs exhibit immunosuppressive functions via diverse mechanisms, including the secretion of anti-inflammatory cytokines and direct cell contact. The balance between Bregs and effector B cells is important for the immune tolerance. In this review, we focus on recent advances in the characteristics of Bregs and their functional roles in autoimmunity. (Source: Frontiers in Immunology)
Source: Frontiers in Immunology - April 15, 2021 Category: Allergy & Immunology Source Type: research

An Integrated Genomic, Proteomic, and Immunopeptidomic Approach to Discover Treatment-Induced Neoantigens
All nucleated mammalian cells express major histocompatibility complex (MHC) proteins that present peptides on cell surfaces for immune surveillance. These MHC-presented peptides (pMHC) are necessary for directing T-cell responses against cells harboring non-self antigens derived from pathogens or from somatic mutations. Alterations in tumor-specific antigen repertoires — particularly novel MHC presentation of mutation-bearing peptides (neoantigens) — can be potent targets of anti-tumor immune responses. Here we employed an integrated genomic and proteomic antigen discovery strategy aimed at measuring how inter...
Source: Frontiers in Immunology - April 15, 2021 Category: Allergy & Immunology Source Type: research