Potential of PINK1 and PARKIN Proteins as Biomarkers for Active Multiple Sclerosis: A Japanese Cohort Study
BackgroundMitochondrial dysfunction has been suggested to play an important role in all stages of multiple sclerosis (MS).ObjectiveTo determine the expression of two mitophagy-related proteins, PTEN-induced kinase 1 (PINK1) and PARKIN, in a cohort of Japanese patients with different neuroinflammatory disorders.MethodsProtein concentrations were measured using commercial ELISA in paired cerebrospinal fluid (CSF) and serum samples from patients with multiple sclerosis (MS), neuromyelitis optica spectrum disorders (NMOSD), and myelin oligodendrocyte glycoprotein antibody disorders (MOGAD), and from age- and sex-matched contro...
Source: Frontiers in Immunology - August 4, 2021 Category: Allergy & Immunology Source Type: research

Cathepsins and Their Endogenous Inhibitors in Host Defense During Mycobacterium tuberculosis and HIV Infection
The moment a very old bacterial pathogen met a young virus from the 80’s defined the beginning of a tragic syndemic for humanity. Such is the case for the causative agent of tuberculosis and the human immunodeficiency virus (HIV). Syndemic is by definition a convergence of more than one disease resulting in magnification of their burden. Both pathogens work synergistically contributing to speed up the replication of each other. Mycobacterium tuberculosis (Mtb) and HIV infections are in the 21st century among the leaders of morbidity and mortality of humankind. There is an urgent need for development of new approaches...
Source: Frontiers in Immunology - August 4, 2021 Category: Allergy & Immunology Source Type: research

The Extracellular NADome Modulates Immune Responses
The term NADome refers to the intricate network of intracellular and extracellular enzymes that regulate the synthesis or degradation of nicotinamide adenine dinucleotide (NAD) and to the receptors that engage it. Traditionally, NAD was linked to intracellular energy production through shuffling electrons between oxidized and reduced forms. However, recent data indicate that NAD, along with its biosynthetic and degrading enzymes, has a life outside of cells, possibly linked to immuno-modulating non-enzymatic activities. Extracellular NAD can engage puriginergic receptors triggering an inflammatory response, similar - to a ...
Source: Frontiers in Immunology - August 4, 2021 Category: Allergy & Immunology Source Type: research

Differential CD147 Functional Epitopes on Distinct Leukocyte Subsets
In this study, we elucidated the functional epitopes on CD147 extracellular domains in T cell regulation using specific monoclonal antibodies (mAbs). Upon T cell activation, the anti-CD147 domain 1 mAbs M6-1E9 and M6-1D4 and the anti-CD147 domain 2 mAb MEM-M6/6 significantly reduced surface expression of CD69 and CD25 and T cell proliferation. To investigate whether functional epitopes of CD147 are differentially expressed on distinct leukocyte subsets, PBMCs, monocyte-depleted PBMCs and purified T cells were activated in the presence of anti-CD147 mAbs. The mAb M6-1E9 inhibited T cell functions via activation of CD147 on ...
Source: Frontiers in Immunology - August 4, 2021 Category: Allergy & Immunology Source Type: research

Therapeutic Response and Possible Biomarkers in Acute Attacks of Neuromyelitis Optica Spectrum Disorders: A Prospective Observational Study
ObjectiveTo explore the outcomes of NMOSD attacks and investigate serum biomarkers for prognosis and severity.MethodPatients with NMOSD attacks were prospectively and observationally enrolled from January 2019 to December 2020 at four hospitals in Guangzhou, southern China. Data were collected at attack, discharge and 1/3/6 months after acute treatment. Serum cytokine/chemokine and neurofilament light chain (NfL) levels were examined at the onset stage.ResultsOne hundred patients with NMOSD attacks were included. The treatment comprised intravenous methylprednisolone pulse therapy alone (IVMP, 71%), IVMP combined with aphe...
Source: Frontiers in Immunology - August 4, 2021 Category: Allergy & Immunology Source Type: research

Visceral Adipose Tissue: A New Target Organ in Virus-Induced Type 1 Diabetes
Type 1 diabetes (T1D) is a proinflammatory pathology that leads to the specific destruction of insulin producing β-cells and hyperglycaemia. Much of the knowledge about type 1 diabetes (T1D) has focused on mechanisms of disease progression such as adaptive immune cells and the cytokines that control their function, whereas mechanisms linked with the initiation of the disease remain unknown. It has been hypothesized that in addition to genetics, environmental factors play a pivotal role in triggering β-cell autoimmunity. The BioBreeding Diabetes Resistant (BBDR) and LEW1.WR1 rats have been used to decipher the mec...
Source: Frontiers in Immunology - August 4, 2021 Category: Allergy & Immunology Source Type: research

PADI2 Polymorphisms Are Significantly Associated With Rheumatoid Arthritis, Autoantibodies Serologic Status and Joint Damage in Women from Southern Mexico
The enzymes of the family peptidylarginine deiminases (PADs) have an important role in the pathogenesis of rheumatoid arthritis (RA) due to their association with the anti-citrullinated protein antibodies (ACPA) production. To evaluate the association between single-nucleotide polymorphisms (SNPs) in the PADI2 gene and RA susceptibility, related clinical parameters, and the serologic status of autoantibodies in a women population with RA from southern Mexico, a case-control study was conducted (case n=229; control n=333). Sociodemographic characteristics were evaluated, along with clinical parameters, inflammation markers,...
Source: Frontiers in Immunology - August 4, 2021 Category: Allergy & Immunology Source Type: research

Gene Set Enrichment Analysis Reveals Individual Variability in Host Responses in Tuberculosis Patients
Group-aggregated responses to tuberculosis (TB) have been well characterized on a molecular level. However, human beings differ and individual responses to infection vary. We have combined a novel approach to individual gene set analysis (GSA) with the clustering of transcriptomic profiles of TB patients from seven datasets in order to identify individual molecular endotypes of transcriptomic responses to TB. We found that TB patients differ with respect to the intensity of their hallmark interferon (IFN) responses, but they also show variability in their complement system, metabolic responses and multiple other pathways. ...
Source: Frontiers in Immunology - August 4, 2021 Category: Allergy & Immunology Source Type: research

ULK1 Inhibition as a Targeted Therapeutic Strategy for Psoriasis by Regulating Keratinocytes and Their Crosstalk With Neutrophils
Psoriasis is a common inflammatory skin disease resulting from an interplay of keratinocytes and immune cells. Previous studies have identified an essential role of autophagy in the maintenance of epidermal homeostasis including proliferation and differentiation. However, much less is known about the role of autophagy-related proteins in the cutaneous immune response. Herein, we showed that ULK1, the key autophagic initiator, and its phosphorylation at Ser556 were distinctively decreased in the epidermis from lesional skin of psoriasis patients. Topical application of SBI0206965, a selective ULK1 inhibitor, significantly a...
Source: Frontiers in Immunology - August 4, 2021 Category: Allergy & Immunology Source Type: research

Intestinal Regulatory T Cells as Specialized Tissue-Restricted Immune Cells in Intestinal Immune Homeostasis and Disease
FOXP3+ regulatory T cells (Treg cells) are a specialized population of CD4+ T cells that restrict immune activation and are essential to prevent systemic autoimmunity. In the intestine, the major function of Treg cells is to regulate inflammation as shown by a wide array of mechanistic studies in mice. While Treg cells originating from the thymus can home to the intestine, the majority of Treg cells residing in the intestine are induced from FOXP3neg conventional CD4+ T cells to elicit tolerogenic responses to microbiota and food antigens. This process largely takes place in the gut draining lymph nodes via interaction wit...
Source: Frontiers in Immunology - August 4, 2021 Category: Allergy & Immunology Source Type: research

Predictive Value of the TP53/PIK3CA/ATM Mutation Classifier for Patients With Bladder Cancer Responding to Immune Checkpoint Inhibitor Therapy
BackgroundOnly a proportion of patients with bladder cancer may benefit from durable response to immune checkpoint inhibitor (ICI) therapy. More precise indicators of response to immunotherapy are warranted. Our study aimed to construct a more precise classifier for predicting the benefit of immune checkpoint inhibitor therapy.MethodsThis multi-cohort study examined the top 20 frequently mutated genes in five cohorts of patients with bladder cancer and developed the TP53/PIK3CA/ATM mutation classifier based on the MSKCC ICI cohort. The classifier was then validated in a validation set consisting of IMvigor210 cohort and Br...
Source: Frontiers in Immunology - August 4, 2021 Category: Allergy & Immunology Source Type: research

Replication/Assembly Defective Avian Flavivirus With Internal Deletions in the Capsid Can Be Used as an Approach for Living Attenuated Vaccine
Avian Tembusu virus (TMUV) is a novel flavivirus causing severe egg drop and fatal encephalitis in avian in Asia. In the present study, we screened the structural and functional requirements of TMUV capsid protein (CP) for viral morphogenesis using reverse genetics methods in combination with replicon packaging assays. TMUV-CP showed dramatic functional and structural flexibility, and even though 44 residues were removed from the N-terminus, it was still capable of packaging replicon RNA; in addition, 33 residues were deleted from the C-terminus (containing nearly the entire α4-helix), and infectious particles were s...
Source: Frontiers in Immunology - August 4, 2021 Category: Allergy & Immunology Source Type: research

Antibody Response to SARS-CoV-2 Membrane Protein in Patients of the Acute and Convalescent Phase of COVID-19
Understanding the course of the antibody response directed to individual epitopes of SARS-CoV-2 proteins is crucial for serological assays and establishment of vaccines. Twenty-one synthetic peptides were synthesized that have ten amino acids overlap and cover the complete membrane (M) protein. Plasma samples from 32 patients having acute disease and 30 patients from the convalescent phase were studied. Only peptide M01 (aa 1–20) and to a lesser extent peptide M21 (aa 201–222) showed specific reactivity as compared to historical control plasma samples. Peptide M01 was recognized by IgM- (71.9%) and IgG-specific...
Source: Frontiers in Immunology - August 4, 2021 Category: Allergy & Immunology Source Type: research

Cooperation Between Systemic IgG1 and Mucosal Dimeric IgA2 Monoclonal Anti-HIV Env Antibodies: Passive Immunization Protects Indian Rhesus Macaques Against Mucosal SHIV Challenges
Understanding the interplay between systemic and mucosal anti-HIV antibodies can provide important insights to develop new prevention strategies. We used passive immunization via systemic and/or mucosal routes to establish cause-and-effect between well-characterized monoclonal antibodies and protection against intrarectal (i.r.) SHIV challenge. In a pilot study, for which we re-used animals previously exposed to SHIV but completely protected from viremia by different classes of anti-HIV neutralizing monoclonal antibodies (mAbs), we made a surprise finding: low-dose intravenous (i.v.) HGN194-IgG1, a human neutralizing mAb a...
Source: Frontiers in Immunology - August 3, 2021 Category: Allergy & Immunology Source Type: research

Comprehensive Characterization of RNA Processing Factors in Gastric Cancer Identifies a Prognostic Signature for Predicting Clinical Outcomes and Therapeutic Responses
This study presents a comprehensive analysis exploring the clinical, molecular, immune, and drug response features underlying the RNA processing factors in GC. This study included 1079 GC cases from The Cancer Genome Atlas (TCGA, training set), our hospital cohort, and two other external validation sets (GSE15459, GSE62254). We developed an RNA processing-related prognostic signature using Cox regression with the least absolute shrinkage and selection operator (LASSO) penalty. The prognostic value of the signature was evaluated using a multiple-method approach. The genetic variants, pathway activation, immune heterogeneity...
Source: Frontiers in Immunology - August 3, 2021 Category: Allergy & Immunology Source Type: research

Inhibition of the Inflammasome Activity of NLRP3 Attenuates HDM-Induced Allergic Asthma
Inhaled allergens promote inflammatory response, tissue damage, and airway hyperresponsiveness in the lungs, leading to allergic asthma. NLRP3, as an immune sensor of infections and cellular stress, is associated with the development and exacerbation of asthma. However, the mechanism by which NLRP3 affects asthma requires further investigation. Here, we showed that inhaled house dust mite (HDM) promotes NLRP3 inflammasome activation in the lungs and specifically induces the maturation of caspase-1 and IL-1β in alveolar macrophages (AMs). Using Nlrp3-mutant mice, we found that NLRP3 promotes the inflammatory response a...
Source: Frontiers in Immunology - August 3, 2021 Category: Allergy & Immunology Source Type: research

Nociceptive Sensory Neurons Mediate Inflammation Induced by Bacillus Anthracis Edema Toxin
Bacterial products are able to act on nociceptive neurons during pathogenic infection. Neurogenic inflammation is an active part of pain signaling and has recently been shown to impact host-pathogen defense. Bacillus anthracis Edema Toxin (ET) produces striking edema in peripheral tissues, but the cellular mechanisms involved in tissue swelling are not completely understood. Here, we find that nociceptive neurons play a role in ET-induced edema and inflammation in mice. Subcutaneous footpad infection of B. anthracis Sterne caused ET-dependent local mechanical allodynia, paw swelling and body weight gain. Subcutaneous admin...
Source: Frontiers in Immunology - August 3, 2021 Category: Allergy & Immunology Source Type: research

GMMA-Based Vaccines: The Known and The Unknown
Generalized Modules for Membrane Antigens (GMMA) are outer membrane vesicles derived from Gram-negative bacteria engineered to provide an over-vesiculating phenotype, which represent an attractive platform for the design of affordable vaccines. GMMA can be further genetically manipulated to modulate the risk of systemic reactogenicity and to act as delivery system for heterologous polysaccharide or protein antigens. GMMA are able to induce strong immunogenicity and protection in animal challenge models, and to be well-tolerated and immunogenic in clinical studies. The high immunogenicity could be ascribed to their particul...
Source: Frontiers in Immunology - August 3, 2021 Category: Allergy & Immunology Source Type: research

Editorial: Employing Experimental Gnotobiotic Models to Decipher the Host-Microbiota Cross-Talk in Health and Disease
(Source: Frontiers in Immunology)
Source: Frontiers in Immunology - August 3, 2021 Category: Allergy & Immunology Source Type: research

Protease-Activation of Fc-Masked Therapeutic Antibodies to Alleviate Off-Tumor Cytotoxicity
We present a novel Fc-tamed antibody format, where the FcγR-binding sites of antibodies are blocked by anti-isotypic masking units, hindering the association of FcγR and complement component 1 (c1q) to the Fc domain. The masking units were genetically fused to trastuzumab, including a protease-addressable peptide-liker. Our Fc-tamed antibodies demonstrated completely abolished interaction to soluble high-affinity Fcγ-Receptor I and c1q. In reporter cell-based ADCC assays, our Fc-tamed antibodies exhibited a 2,700 to 7,100-fold reduction in activation, compared to trastuzumab. Upon demasking by a tumor-ass...
Source: Frontiers in Immunology - August 3, 2021 Category: Allergy & Immunology Source Type: research

Mycobacterium-Induced Th1, Helminths-Induced Th2 Cells and the Potential Vaccine Candidates for Allergic Asthma: Imitation of Natural Infection
Bronchial asthma is one of the most chronic pulmonary diseases and major public health problems. In general, asthma prevails in developed countries than developing countries, and its prevalence is increasing in the latter. For instance, the hygiene hypothesis demonstrated that this phenomenon resulted from higher household hygienic standards that decreased the chances of infections, which would subsequently increase the occurrence of allergy. In this review, we attempted to integrate our knowledge with the hygiene hypothesis into beneficial preventive approaches for allergic asthma. Therefore, we highlighted the studies th...
Source: Frontiers in Immunology - August 3, 2021 Category: Allergy & Immunology Source Type: research

Identification of a Hematopoietic Cell Population Emerging From Mouse Bone Marrow With Proliferative Potential In Vitro and Immunomodulatory Capacity
In conclusion, bone marrow contains two cell populations with immunomodulatory properties, which are valuable sources for therapeutic studies in specific disease-relevant contexts. (Source: Frontiers in Immunology)
Source: Frontiers in Immunology - August 3, 2021 Category: Allergy & Immunology Source Type: research

Placental Immune Tolerance and Organ Transplantation: Underlying Interconnections and Clinical Implications
The immune system recognizes and attacks non-self antigens, making up the cornerstone of immunity activity against infection. However, during organ transplantation, the immune system also attacks transplanted organs and leads to immune rejection and transplantation failure. Interestingly, although the embryo and placenta are semi-allografts, like transplanted organs, they can induce maternal tolerance and be free of a vigorous immune response. Also, embryo or placenta-related antibodies might adversely affect subsequent organ transplantation despite the immune tolerance during pregnancy. Therefore, the balance between the ...
Source: Frontiers in Immunology - August 3, 2021 Category: Allergy & Immunology Source Type: research

Case Report: Acquired Disseminated BCG in the Context of a Delayed Immune Reconstitution After Hematological Malignancy
ConclusionThis case highlights the fact that, in addition to the IEI, physicians, as well as microbiologists and pharmacists should be aware of possible acquired disseminated BCG disease in secondary immunocompromised patients treated in centers that administrate BCG for bladder cancers. (Source: Frontiers in Immunology)
Source: Frontiers in Immunology - August 3, 2021 Category: Allergy & Immunology Source Type: research

BMP4 Moderates Glycolysis and Regulates Activation and Interferon-Gamma Production in CD4+ T Cells
BMP4 is a key growth factor well known in promoting bone regeneration and has been reported to be able to regulate T cell development in the thymus. Here, we showed that BMP4 downregulates the activation of naïve CD4+ T cells and the IFN-γ production of CD4+ T cells without increasing regulatory T cells. BMP4 could also moderate glycolysis of T cells and regulate Hif1α expression. Furthermore, BMP4 showed a suppressive function on the IFN-γ production of CD4+ T cells in vivo. These findings indicating a mechanism by which BMP-4 may regulate activation and IFN-γ production in CD4+ T cells via me...
Source: Frontiers in Immunology - August 3, 2021 Category: Allergy & Immunology Source Type: research

Granzyme A Produced by γ9δ2 T Cells Activates ER Stress Responses and ATP Production, and Protects Against Intracellular Mycobacterial Replication Independent of Enzymatic Activity
Mycobacterium tuberculosis (Mtb), the pathological agent that causes tuberculosis (TB) is the number one infectious killer worldwide with one fourth of the world’s population currently infected. Data indicate that γ9δ2 T cells secrete Granzyme A (GzmA) in the extracellular space triggering the infected monocyte to inhibit growth of intracellular mycobacteria. Accordingly, deletion of GZMA from γ9δ2 T cells reverses their inhibitory capacity. Through mechanistic studies, GzmA’s action was investigated in monocytes from human PBMCs. The use of recombinant human GzmA expressed in a mammalia...
Source: Frontiers in Immunology - August 3, 2021 Category: Allergy & Immunology Source Type: research

The Transcriptomic Profile of Monocytes from Patients With Sj ögren’s Syndrome Is Associated With Inflammatory Parameters and Is Mimicked by Circulating Mediators
Primary Sjögren’s syndrome (pSS) is a systemic autoimmune disease characterized by infiltration of the exocrine glands and prominent B cell hyperactivity. Considering the key role of monocytes in promoting B cell hyperactivity, we performed RNA-sequencing analysis of CD14+ monocytes from patients with pSS, non-Sjögren’s sicca (nSS), and healthy controls (HC). We demonstrated that the transcriptomic profile of pSS patients is enriched in intermediate and non-classical monocyte profiles, and confirmed the increased frequency of non-classical monocytes in pSS patients by flow-cytometry analysis. Weighted...
Source: Frontiers in Immunology - August 3, 2021 Category: Allergy & Immunology Source Type: research

LPSlow-Macrophages Alleviate the Outcome of Graft-Versus-Host Disease Without Aggravating Lymphoma Growth in Mice
Despite significant therapeutic advances, graft-versus-host disease (GvHD) remains the main life-threatening complication following allogeneic hematopoietic stem cell transplantation. The pathogenesis of GvHD is dominated by a dysregulated allogeneic immune response that drives fibrosis and autoimmunity in chronic forms. A multitude of cell therapy approaches, including infusion of myeloid cells, has been proposed to prevent GvHD through tolerance induction but yielded variable results. Myeloid cells like macrophages can be reprogrammed to develop adaptive-like features following antigenic challenge to reinforce or inhibit...
Source: Frontiers in Immunology - August 3, 2021 Category: Allergy & Immunology Source Type: research

Novel Immune Cell-Based Therapies to Eradicate High-Risk Acute Myeloid Leukemia
Adverse genetic risk acute myeloid leukemia (AML) includes a wide range of clinical-pathological entities with extremely poor outcomes; thus, novel therapeutic approaches are needed. Promising results achieved by engineered chimeric antigen receptor (CAR) T cells in other blood neoplasms have paved the way for the development of immune cell-based therapies for adverse genetic risk AML. Among these, adoptive cell immunotherapies with single/multiple CAR-T cells, CAR-natural killer (NK) cells, cytokine-induced killer cells (CIK), and NK cells are subjects of ongoing clinical trials. On the other hand, allogeneic hematopoieti...
Source: Frontiers in Immunology - August 3, 2021 Category: Allergy & Immunology Source Type: research

Case Report: Abscopal Effect of Microwave Ablation in a Patient With Advanced Squamous NSCLC and Resistance to Immunotherapy
Currently, immunotherapy has been a backbone in the treatment of advanced non-small cell lung cancer (NSCLC) without driver gene mutations. However, only a small proportion of NSCLC patients respond to immune checkpoint inhibitors, and majority of patients with initial response will develop acquired resistance at 5 years, which usually manifests as oligo-progression or oligo-metastases. Evidence from multiple clinical trials indicates that local consolidative therapies could improve the prognosis of oligometastatic NSCLC patients. Herein, we reported a case of advanced squamous lung cancer which showed a durable abscopal e...
Source: Frontiers in Immunology - August 3, 2021 Category: Allergy & Immunology Source Type: research

Editorial: The Present and Future of Immunology Education
(Source: Frontiers in Immunology)
Source: Frontiers in Immunology - August 2, 2021 Category: Allergy & Immunology Source Type: research

Phosphorylation of Shrimp Tcf by a Viral Protein Kinase WSV083 Suppresses Its Antiviral Effect
Nuclear DNA-binding TCF proteins, which act as the main downstream effectors of Wnt signaling, are essential for the regulation of cell fate and innate immunity. However, their role during viral infection in shrimp remains unknown. Herein, we demonstrated that Litopenaeus vannamei TCF (LvTcf) acts independently of Lvβ-catenin to promote interferon-like protein LvVago1 production, thus mounting the response to WSSV infection. Further, we observed that WSV083, a WSSV serine/threonine protein kinase, bound to LvTcf and phosphorylated it. Phosphorylated LvTcf was then recognized and degraded via the ubiquitin-proteasome p...
Source: Frontiers in Immunology - August 2, 2021 Category: Allergy & Immunology Source Type: research

The Optimal Second-Line Systemic Treatment Model for Recurrent and/or Metastatic Head and Neck Squamous Cell Carcinoma: A Bayesian Network Meta-Analysis
ConclusionFor R/M HNSCC patients without immune checkpoint inhibitors in the first-line setting, SI may serve as the optimal second-line systemic treatment model, demonstrating the best OS and least sAE. (Source: Frontiers in Immunology)
Source: Frontiers in Immunology - August 2, 2021 Category: Allergy & Immunology Source Type: research

Case Report: C-Reactive Protein Apheresis in a Patient With COVID-19 and Fulminant CRP Increase
ConclusionThis is the first report on CRP apheresis in an early COVID-19 patient with fulminant CRP increase. Despite a poor prognosis due to his diabetes and biomarker profile, the patient was not ventilated, and the onset of pneumonia was reverted. (Source: Frontiers in Immunology)
Source: Frontiers in Immunology - August 2, 2021 Category: Allergy & Immunology Source Type: research

Immunological Involvement of MicroRNAs in the Key Events of Systemic Lupus Erythematosus
Systemic lupus erythematosus (SLE) is an archetype autoimmune disease characterized by a myriad of immunoregulatory abnormalities that drives injury to multiple tissues and organs. Due to the involvement of various immune cells, inflammatory cytokines, and related signaling pathways, researchers have spent a great deal of effort to clarify the complex etiology and pathogenesis of SLE. Nevertheless, current understanding of the pathogenesis of SLE is still in the early stages, and available nonspecific treatment options for SLE patients remain unsatisfactory. First discovered in 1993, microRNAs (miRNAs) are small RNA molecu...
Source: Frontiers in Immunology - August 2, 2021 Category: Allergy & Immunology Source Type: research

Plasma C-Reactive Protein and Pentraxin-3 Reference Intervals During Normal Pregnancy
Although several biomarkers are available to monitor the acute phase response, the short pentraxin C-reactive protein (CRP) is dominating in clinical practice. The long pentraxin 3 (PTX3) is structurally and functionally related to CRP, but not liver-derived. In addition, increased levels of PTX3 have been linked to preeclampsia. Reference intervals are usually based on healthy blood donors. Several physiological and immunological alterations occur during normal pregnancy with subsequent potential effects on blood analytes. Hence, this study aims to determine pregnancy-specific reference intervals for CRP and PTX3. Longitu...
Source: Frontiers in Immunology - August 2, 2021 Category: Allergy & Immunology Source Type: research

Mannose Receptor Mediates the Activation of Chitooligosaccharides on Blunt Snout Bream (Megalobrama amblycephala) Macrophages
In this study, we further explored the internalization mechanism and signal transduction pathway of chitooligosaccharide hexamer (COS6) in blunt snout bream macrophages. The results showed that mannose receptor C-type lectin-like domain 4-8 of M. amblycephala (MaMR CTLD4-8) could recognize and bind to COS6 and mediate COS6 into macrophages by both clathrin-dependent and caveolin-dependent pathways. In the inflammatory response of macrophages activated by COS6, the gene expression of tumor necrosis factor (TNF)-α, interleukin (IL)-1β, and nitric oxide synthase 2 (NOS2) was significantly inhibited after MaMR CTLD4...
Source: Frontiers in Immunology - August 2, 2021 Category: Allergy & Immunology Source Type: research

Long Noncoding RNAs as Emerging Regulators of COVID-19
Coronavirus disease 2019 (COVID-19), which has high incidence rates with rapid rate of transmission, is a pandemic that spread across the world, resulting in more than 3,000,000 deaths globally. Currently, several drugs have been used for the clinical treatment of COVID-19, such as antivirals (radecivir, baritinib), monoclonal antibodies (tocilizumab), and glucocorticoids (dexamethasone). Accumulating evidence indicates that long noncoding RNAs (lncRNAs) are essential regulators of virus infections and antiviral immune responses including biological processes that are involved in the regulation of COVID-19 and subsequ...
Source: Frontiers in Immunology - August 2, 2021 Category: Allergy & Immunology Source Type: research

Vitamin D Inhibits IL-22 Production Through a Repressive Vitamin D Response Element in the il22 Promoter
Th22 cells constitute a recently described CD4+ T cell subset defined by its production of interleukin (IL)-22. The action of IL-22 is mainly restricted to epithelial cells. IL-22 enhances keratinocyte proliferation but inhibits their differentiation and maturation. Dysregulated IL-22 production has been associated to some inflammatory skin diseases such as atopic dermatitis and psoriasis. How IL-22 production is regulated in human T cells is not fully known. In the present study, we identified conditions to generate Th22 cells that do not co-produce IL-17 from naïve human CD4+ T cells. We show that in addition to the...
Source: Frontiers in Immunology - August 2, 2021 Category: Allergy & Immunology Source Type: research

Fast and Efficient Genome Editing of Human FOXP3+ Regulatory T Cells
FOXP3+ regulatory T cells (Tregs) are central for maintaining peripheral tolerance and immune homeostasis. Because of their immunosuppressive characteristics, Tregs are a potential therapeutic target in various diseases such as autoimmunity, transplantation and infectious diseases like COVID-19. Numerous studies are currently exploring the potential of adoptive Treg therapy in different disease settings and novel genome editing techniques like CRISPR/Cas will likely widen possibilities to strengthen its efficacy. However, robust and expeditious protocols for genome editing of human Tregs are limited. Here, we describe...
Source: Frontiers in Immunology - August 2, 2021 Category: Allergy & Immunology Source Type: research

Activated, Pro-Inflammatory Th1, Th17, and Memory CD4+ T Cells and B Cells Are Involved in Delayed-Type Hypersensitivity Arthritis (DTHA) Inflammation and Paw Swelling in Mice
Delayed-type hypersensitivity arthritis (DTHA) is a recently established experimental model of rheumatoid arthritis (RA) in mice with pharmacological values. Despite an indispensable role of CD4+ T cells in inducing DTHA, a potential role for CD4+ T cell subsets is lacking. Here we have quantified CD4+ subsets during DTHA development and found that levels of activated, pro-inflammatory Th1, Th17, and memory CD4+ T cells in draining lymph nodes were increased with differential dynamic patterns after DTHA induction. Moreover, according to B-cell depletion experiments, it has been suggested that this cell type is not involved...
Source: Frontiers in Immunology - August 2, 2021 Category: Allergy & Immunology Source Type: research

Preliminary Safety and Potential Effect of 6B11-OCIK Adoptive Cell Therapy Against Platinum-Resistant Recurrent or Refractory Ovarian Cancer
Ovarian cancer is a leading cause of death among gynecological malignancies, and novel therapies are urgently needed. Here we report preliminary findings on the potential safety and efficacy of 6B11-OCIK, an adoptive cell therapy of autologous T cells induced by the humanized anti-idiotypic antibody 6B11 minibody plus dendritic cells and cytokines, against platinum-resistant recurrent or refractory ovarian cancer in three patients. We found that 6B11-OCIK treatment was safe and well tolerated after five cycles of intravenous infusion with an initial dose of 1–2×109 cells and a dose-climbing strategy. Hemoglobin...
Source: Frontiers in Immunology - August 2, 2021 Category: Allergy & Immunology Source Type: research

Vaccination in Children With Autoimmune Disorders and Treated With Various Immunosuppressive Regimens: A Comprehensive Review and Practical Guide
Children with autoimmune disorders are especially at risk of vaccine-preventable diseases due to their underlying disease and the immunosuppressive treatment often required for a long period. In addition, vaccine coverage remains too low in this vulnerable population. This can be explained by a fear of possible adverse effects of vaccines under immunosuppression, but also a lack of data and clear recommendations, particularly with regard to vaccination with live vaccines. In this review, the latest literature and recommendations on vaccination in immunosuppressed children are discussed in detail, with the aim to provide a ...
Source: Frontiers in Immunology - August 2, 2021 Category: Allergy & Immunology Source Type: research

Gut Microbiome and Common Variable Immunodeficiency: Few Certainties and Many Outstanding Questions
Common variable immunodeficiency (CVID) is the most common symptomatic primary antibody immunodeficiency, characterized by reduced serum levels of IgG, IgA, and/or IgM. The vast majority of CVID patients have polygenic inheritance. Immune dysfunction in CVID can frequently involve the gastrointestinal tract and lung. Few studies have started to investigate the gut microbiota profile in CVID patients. Overall, the results suggest that in CVID patients there is a reduction of alpha and beta diversity compared to controls. In addition, these patients can exhibit increased plasma levels of lipopolysaccharide (LPS) and markers ...
Source: Frontiers in Immunology - August 2, 2021 Category: Allergy & Immunology Source Type: research

Efficacy of Thymosin Alpha 1 in the Treatment of COVID-19: A Multicenter Cohort Study
This study aimed to explore the efficacy of Tα1 as a COVID-19 therapy.MethodsWe performed a multicenter cohort study in five tertiary hospitals in the Hubei province of China between December 2019 and March 2020. The patient non-recovery rate was used as the primary outcome.ResultsAll crude outcomes, including non-recovery rate (65/306 vs. 290/1,976, p = 0.003), in-hospital mortality rate (62/306 vs. 271/1,976, p = 0.003), intubation rate (31/306 vs. 106/1,976, p = 0.001), acute respiratory distress syndrome (ARDS) incidence (104/306 vs. 499/1,976, p = 0.001), acute kidney injury (AKI) incidence (26/306 vs. 66/1,976, p
Source: Frontiers in Immunology - August 2, 2021 Category: Allergy & Immunology Source Type: research

Editorial: The Role of Platelet Activation in the Pathophysiology of HIV, Tuberculosis and Pneumococcal Disease
(Source: Frontiers in Immunology)
Source: Frontiers in Immunology - July 30, 2021 Category: Allergy & Immunology Source Type: research

Sclerosing Sialadenitis Is Associated With Salivary Gland Hypofunction and a Unique Gene Expression Profile in Sj ögren’s Syndrome
ConclusionRIFA quantification is a novel method for assessing interstitial fibrosis and the impact of fibrosis on SS symptoms. Loss of gland function may be associated with salivary gland fibrosis, which is likely to be driven by a unique set of genes that are mainly expressed by fibroblasts. (Source: Frontiers in Immunology)
Source: Frontiers in Immunology - July 30, 2021 Category: Allergy & Immunology Source Type: research

Melioidosis Patient Survival Correlates With Strong IFN- γ Secreting T Cell Responses Against Hcp1 and TssM
This study was aimed at evaluating human cellular and humoral immune responses in Thai adults against four melioidosis vaccine candidate antigens. Blood samples from 91 melioidosis patients and 100 healthy donors from northeast Thailand were examined for immune responses against B. pseudomallei Hcp1, AhpC, TssM and LolC using a variety of cellular and humoral immune assays including IFN-γ ELISpot assays, flow cytometry and ELISA. PHA and a CPI peptide pool were also used as control stimuli in the ELISpot assays. Hcp1 and TssM stimulated strong IFN-γ secreting T cell responses in acute melioidosis patients which...
Source: Frontiers in Immunology - July 30, 2021 Category: Allergy & Immunology Source Type: research

Editorial: Intestinal Dysbiosis in Inflammatory Diseases
(Source: Frontiers in Immunology)
Source: Frontiers in Immunology - July 30, 2021 Category: Allergy & Immunology Source Type: research

Single-Cell Transcriptomic Profiling of MAIT Cells in Patients With COVID-19
ConclusionsThe results of the present study suggest that MAIT cells are likely to be involved in the host immune response against SARS-CoV-2 infection. Simultaneously, the transcriptomic data from MAIT cells provides a deeper understanding of the immune pathogenesis of the disease. (Source: Frontiers in Immunology)
Source: Frontiers in Immunology - July 30, 2021 Category: Allergy & Immunology Source Type: research