scholarly journals Food antigens drive spontaneous IgE elevation in the absence of commensal microbiota

2019 ◽  
Vol 5 (5) ◽  
pp. eaaw1507 ◽  
Author(s):  
Sung-Wook Hong ◽  
Eunju O ◽  
Jun Young Lee ◽  
Minji Lee ◽  
Daehee Han ◽  
...  
Keyword(s):  
Early Life ◽  
Immunoglobulin E ◽  
Allergic Diseases ◽  
Lymphoid Tissues ◽  
T Helper 2 ◽  
Commensal Microbiota ◽  
Follicular Helper ◽  
Food Antigen ◽  
Food Antigens ◽  
Underlying Mechanisms

Immunoglobulin E (IgE), a key mediator in allergic diseases, is spontaneously elevated in mice with disrupted commensal microbiota such as germ-free (GF) and antibiotics-treated mice. However, the underlying mechanisms for aberrant IgE elevation are still unclear. Here, we demonstrate that food antigens drive spontaneous IgE elevation in GF and antibiotics-treated mice by generating T helper 2 (TH2)–skewed T follicular helper (TFH) cells in gut-associated lymphoid tissues (GALTs). In these mice, depriving contact with food antigens results in defective IgE elevation as well as impaired generation of TFH cells and IgE-producing cells in GALT. Food antigen–driven TFH cells in GF mice are mostly generated in early life, especially during the weaning period. We also reveal that food antigen–driven TFH cells in GF mice are actively depleted by colonization with commensal microbiota. Thus, our findings provide a possible explanation for why the perturbation of commensal microbiota in early life increases the occurrence of allergic diseases.

scholarly journals Atypical Food protein-induced enterocolitis syndrome in children: Is IgE sensitization an issue longitudinally?

2021 ◽  
Vol 49 (3) ◽  
pp. 73-82
Author(s):  
Athina Papadopoulou ◽  
Theano Lagousi ◽  
Elpiniki Hatzopoulou ◽  
Paraskevi Korovessi ◽  
Stavroula Kostaridou ◽  
...  
Keyword(s):  
Immunoglobulin E ◽  
Allergic Diseases ◽  
Cow’S Milk ◽  
Food Protein ◽  
Cow's Milk ◽  
T Helper 2 ◽  
Term Evaluation ◽  
Ige Mediated ◽  
Trigger Mechanisms

Background: Food Protein-Induced Enterocolitis Syndrome (FPIES) is a clinically well-characterised, non-Immunoglobulin E (IgE)-mediated food allergy syndrome, yet its rare atypical presen-tation remains poorly understood.Objective: Aim of this study was to present the 10-year experience of a referral centre high-lighting the atypical FPIES cases and their long-term outcome.Methods: FPIES cases were prospectively evaluated longitudinally in respect of food outgrowth and developing other allergic diseases with or without concomitant IgE sensitisation.Results: One hundred subjects out of a total of 14,188 referrals (0.7%) were identified. At pre-sentation, 15 patients were found sensitised to the offending food. Fish was the most frequent eliciting food, followed by cow’s milk and egg. Tolerance acquisition was earlier for cow’s milk, followed by egg and fish, while found not to be protracted in atypical cases. Resolution was not achieved in half of the fish subjects during the 10-year follow-up time. Sensitisation to food was not related to infantile eczema or culprit food, but was related to sensitisation to aeroallergens. In the long-term evaluation, persistence of the FPIES or aeroallergen sensitisation was significantly associated with an increased hazard risk of developing early asthma symptoms. Conclusion: Sensitisation to food was related neither to eczema or culprit food nor to tolerance acquisition but rather to the development of allergic asthma through aeroallergen sen-sitisation. In addition to an IgE profile at an early age, FPIES persistence may also trigger mechanisms switching FPIES cases to a T-helper 2 cells immune response later in life, predis-posing to atopic respiratory symptoms; albeit further research is required.

scholarly journals DNA Methylation at Birth is Associated with Childhood Serum Immunoglobulin E Levels

2021 ◽  
Vol 14 ◽  
pp. 251686572110081
Author(s):  
Luhang Han ◽  
Akhilesh Kaushal ◽  
Hongmei Zhang ◽  
Latha Kadalayil ◽  
Jiasong Duan ◽  
...  
Keyword(s):  
Dna Methylation ◽  
Gene Ontology ◽  
Cord Blood ◽  
Early Life ◽  
Immunoglobulin E ◽  
Allergic Diseases ◽  
Total Serum ◽  
Gene Ontology Analysis ◽  
Serum Ige ◽  
Cpg Sites

Immunoglobulin E (IgE) is known to play an important role in allergic diseases. Epigenetic traits acquired due to modification of deoxyribonucleic acid (DNA) methylation (DNAm) in early life may have phenotypic consequences through their role in transcriptional regulation with relevance to the developmental origins of diseases including allergy. However, epigenome-scale studies on the longitudinal association of cord blood DNAm with IgE over time are lacking. Our study aimed to examine the association of DNAm at birth with childhood serum IgE levels during early life. Genome-scale DNAm and total serum IgE measured at birth, 5, 8, and 11 years of children in the Taiwan Maternal and Infant Cohort Study were included in the study in the discovery stage. Linear mixed models were implemented to assess the association between cord blood DNAm at ~310K 5′-cytosine-phosphate-guanine-3′ (CpG) sites with repeated IgE measurements, adjusting for cord blood IgE. Identified statistically significant CpGs (at a false discovery rate, FDR, of 0.05) were further tested in an independent replication cohort, the Isle of Wight (IoW) birth cohort. We mapped replicated CpGs to genes and conducted gene ontology analysis using ToppFun to identify significantly enriched pathways and biological processes of the genes. Cord blood DNAm of 273 CpG sites were significantly (FDR = 0.05) associated with IgE levels longitudinally. Among the identified CpGs available in both cohorts (184 CpGs), 92 CpGs (50%) were replicated in the IoW in terms of consistency in direction of associations between DNA methylation and IgE levels later in life, and 16 of the 92 CpGs showed statistically significant associations ( P < .05). Gene ontology analysis identified 4 pathways (FDR = 0.05). The identified 16 CpG sites had the potential to serve as epigenetic markers associated with later IgE production, beneficial to allergic disease prevention and intervention.

scholarly journals Immunologic Pathophysiology and Airway Remodeling Mechanism in Severe Asthma: Focused on IgE-Mediated Pathways

Diagnostics ◽  
2021 ◽  
Vol 11 (1) ◽  
pp. 83
Author(s):  
Shih-Lung Cheng
Keyword(s):  
Severe Asthma ◽  
Immunoglobulin E ◽  
Airway Remodeling ◽  
Real Life ◽  
Allergic Diseases ◽  
Proinflammatory Mediators ◽  
Small Subgroup ◽  
Humanized Monoclonal Antibody ◽  
Severe Allergic Asthma ◽  
Ige Mediated

Despite the expansion of the understanding in asthma pathophysiology and the continual advances in disease management, a small subgroup of patients remains partially controlled or refractory to standard treatments. Upon the identification of immunoglobulin E (IgE) and other inflammatory mediators, investigations and developments of targeted agents have thrived. Omalizumab is a humanized monoclonal antibody that specifically targets the circulating IgE, which in turn impedes and reduces subsequent releases of the proinflammatory mediators. In the past decade, omalizumab has been proven to be efficacious and well-tolerated in the treatment of moderate-to-severe asthma in both trials and real-life studies, most notably in reducing exacerbation rates and corticosteroid use. While growing evidence has demonstrated that omalizumab may be potentially beneficial in treating other allergic diseases, its indication remains confined to treating severe allergic asthma and chronic idiopathic urticaria. Future efforts may be bestowed on determining the optimal length of omalizumab treatment, seeking biomarkers that could better predict treatment response and as well as extending its indications.

scholarly journals Allergic diseases attributable to atopy in a population sample of Asian children

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Chao-Yi Wu ◽  
Hsin-Yi Huang ◽  
Wen-Chi Pan ◽  
Sui-Ling Liao ◽  
Man-Chin Hua ◽  
...  
Keyword(s):  
Immunoglobulin E ◽  
Population Attributable Risk ◽  
Population Sample ◽  
International Study ◽  
Allergic Diseases ◽  
Population Based ◽  
School Age Children ◽  
Specific Immunoglobulin E ◽  
Asian Children ◽  
Specific Immunoglobulin

AbstractThe proportion of allergic diseases attributable to atopy remains a subject of controversy. This study aimed to estimate the population risk of physician-diagnosed asthma, rhinitis and eczema attributed to atopy among a population sample of Asian school-age children. Asian children aged 5–18 years (n = 1321) in the Prediction of Allergies in Taiwanese CHildren (PATCH) study were tested for serum allergen-specific immunoglobulin E. Physician-diagnosed asthma, rhinitis and eczema were assessed by a modified International Study of Asthma and Allergies in Childhood questionnaire. Atopy was defined as the presence of serum allergen-specific immunoglobulin E. In this population-based study, 50.4% of the subjects with asthma, 46.3% with rhinitis, and 46.7% with eczema were attributable to atopy. The population attributable risk (PAR) of atopy for three allergic diseases was higher in adolescents (asthma, 54.4%; rhinitis, 59.6%; eczema, 49.5%) than younger children aged less than 10 years (asthma, 46.9%; rhinitis, 39.5%; eczema, 41.9%). Among the seven allergen categories, sensitization to mites had the highest PARs for all three allergic diseases (51.3 to 64.1%), followed by sensitization to foods (asthma, 7.1%; rhinitis, 10.4%; eczema 27.7%). In conclusion, approximately half (46.3 to 50.4%) of Asian children in Taiwan with allergic diseases are attributable to atopy.

scholarly journals Melatonin Successfully Rescues the Hippocampal Molecular Machinery and Enhances Anti-oxidative Activity Following Early-Life Sleep Deprivation Injury

Antioxidants ◽  
2021 ◽  
Vol 10 (5) ◽  
pp. 774
Author(s):  
Hung-Ming Chang ◽  
Hsing-Chun Lin ◽  
Hsin-Lin Cheng ◽  
Chih-Kai Liao ◽  
To-Jung Tseng ◽  
...  
Keyword(s):  
Sleep Deprivation ◽  
Early Life ◽  
Cognitive Activity ◽  
Oxidative Activity ◽  
Protective Effects ◽  
Long Term Effects ◽  
Ionic Distribution ◽  
Melatonin Administration ◽  
Molecular Machinery ◽  
Underlying Mechanisms

Early-life sleep deprivation (ESD) is a serious condition with severe cognitive sequelae. Considering hippocampus plays an essential role in cognitive regulation, the present study aims to determine whether melatonin, a neuroendocrine beard with significant anti-oxidative activity, would greatly depress the hippocampal oxidative stress, improves the molecular machinery, and consequently exerts the neuro-protective effects following ESD. Male weanling Wistar rats (postnatal day 21) were subjected to ESD for three weeks. During this period, the animals were administered normal saline or melatonin (10 mg/kg) via intraperitoneal injection between 09:00 and 09:30 daily. After three cycles of ESD, the animals were kept under normal sleep/wake cycle until they reached adulthood and were sacrificed. The results indicated that ESD causes long-term effects, such as impairment of ionic distribution, interruption of the expressions of neurotransmitters and receptors, decreases in the levels of several antioxidant enzymes, and impairment of several signaling pathways, which contribute to neuronal death in hippocampal regions. Melatonin administration during ESD prevented these effects. Quantitative evaluation of cells also revealed a higher number of neurons in the melatonin-treated animals when compared with the saline-treated animals. As the hippocampus is critical to cognitive activity, preserving or even improving the hippocampal molecular machinery by melatonin during ESD not only helps us to better understand the underlying mechanisms of ESD-induced neuronal dysfunction, but also the therapeutic use of melatonin to counteract ESD-induced neuronal deficiency.

Early-life inflammation primes a T helper 2 cell–fibroblast niche in skin

Nature ◽  
2021 ◽  
Author(s):  
Ian C. Boothby ◽  
Maxime J. Kinet ◽  
Devi P. Boda ◽  
Elaine Y. Kwan ◽  
Sean Clancy ◽  
...  
Keyword(s):  
Early Life ◽  
T Helper ◽  
T Helper 2

scholarly journals CCR6–CCL20-Mediated Immunologic Pathways in Inflammatory Bowel Disease

2018 ◽  
Vol 1 (1) ◽  
pp. 15-29 ◽  
Author(s):  
Ranmali Ranasinghe ◽  
Rajaraman Eri
Keyword(s):  
Inflammatory Bowel Disease ◽  
Bowel Disease ◽  
Intestinal Inflammation ◽  
Systematic Investigation ◽  
Protective Mechanism ◽  
Food Antigens ◽  
Gut Mucosa ◽  
T Helper Lymphocyte ◽  
Inflammatory Bowel ◽  
Underlying Mechanisms

Inflammatory bowel disease (IBD) has evoked significant interest in human immunobiology given its tactical immune evasion methodologies resulting in acute immune destabilization. IBD comprising Crohn’s disease and Ulcerative colitis manifests as chronic inflammation in the gut mucosa, leading to complexities involving immune dysregulation in the T helper lymphocyte arm, effecting disease pathogenicity. The mucosa of the alimentary canal is constantly exposed to a myriad of food antigens and luminal microorganisms for which a consistent host-protective mechanism is operative in healthy people. Lowered mucosal immune expression which allows penetration of the epithelial barrier by infective pathogenic microbes elicits both innate and adaptive immune responses in the gut, culminating in aberrant intestinal inflammation. Interestingly, the IBD leukocyte repertoire is significantly entwined with chemokine-assisted chemotactic navigation into the sites of inflammation, which is also thought to generate favorable immune-suppressive responses. The functions of the cognate chemokine receptor, CCR6, which binds with its unique ligand CCL20, are expected to tilt the balance between upregulation of homeostatic tolerance and inflammatory pathophysiology. This review aims to critically examine the CCR6-driven immune pathways: TH1/TH2, TH1/TH17, TH17/Treg, IL-23/IL-17, Akt/ERK-1/2, ILC3, and TH9/TH2 for systematic investigation of its underlying mechanisms in the future and to underpin its importance in resolving IBD pathology. Thus, CCR6 occupies an exclusive position in gut immunology which renders it an invaluable therapeutic tool for the production of novel medicaments to treat IBD.

scholarly journals A new look at IgE beyond allergies

F1000Research ◽  
2019 ◽  
Vol 8 ◽  
pp. 736 ◽  
Author(s):  
Andrea J. Luker ◽  
Joseph C. Lownik ◽  
Daniel H. Conrad ◽  
Rebecca K. Martin
Keyword(s):  
Immunoglobulin E ◽  
Atopic Disease ◽  
Organ Damage ◽  
Vital Role ◽  
Immune Recognition ◽  
Th2 Response ◽  
Effector Cells ◽  
T Helper 2 ◽  
Disease States ◽  
Ige Response

Immunoglobulin E (IgE), though constitutively present at low levels, is most commonly studied in atopic disease where it plays a vital role in mast cell degranulation and in initiating a T helper 2 (Th2) response. With the advent of better detection assays, however, researchers are discovering the importance of IgE in actively contributing to many disease states and pathologies. This review will discuss the latest findings in IgE beyond its role in allergies and recently discovered roles for IgE in its cell-bound form on FcεRI-expressing effector cells like monocytes and dendritic cells. In terms of parasites, we will discuss helminth-induced IgE that appears to protect the worms from immune recognition and a tick-borne illness that elicits an IgE response against red meat. Next, we describe recent findings of how auto-reactive IgE can contribute to the progression of lupus and induce organ damage. Finally, we summarize the emerging roles of IgE in tumor surveillance and antibody-dependent cytotoxicity. We additionally discuss recent or ongoing clinical trials that either target harmful IgE or use the unique characteristics of the isotype.

scholarly journals Born to be young: prenatal thyroid hormones increase early-life telomere length

2020 ◽  
Author(s):  
Antoine Stier ◽  
Bin-Yan Hsu ◽  
Coline Marciau ◽  
Blandine Doligez ◽  
Lars Gustafsson ◽  
...  
Keyword(s):  
Thyroid Hormones ◽  
Telomere Length ◽  
Early Life ◽  
Copy Number ◽  
Growth Period ◽  
Postnatal Growth ◽  
Mtdna Copy Number ◽  
Underlying Mechanisms ◽  
Growth And Aging ◽  
Positive Effect

AbstractPrenatal environmental conditions can have lifelong consequences on health and aging. The underlying mechanisms remain nonetheless little understood. Thyroid hormones (THs) are important regulators of embryogenesis transferred from the mother to the embryo. In an avian model, we manipulated embryo exposure to maternal THs through egg injection and investigated the consequences on postnatal growth and aging. We first report that mitochondrial DNA (mtDNA) copy number and telomere length significantly decrease from early-life to late adulthood, thus confirming that these two molecular markers are hallmarks of aging in our wild bird model. The experimental elevation of prenatal THs levels had a transient positive effect on postnatal growth. Elevated prenatal THs had no effect on mtDNA copy number but significantly increased telomere length both soon after birth and at the end of the growth period (equivalent to offsetting ca. 4 years of post-growth telomere shortening). These findings suggest that prenatal THs have a key role in setting the ‘biological’ age at birth, and thus might influence longevity.

scholarly journals High-Dimensional Immunophenotyping of Murine T-cell and B-cell Subsets

2020 ◽  
Author(s):  
Kyle T. Mincham ◽  
Jacob D. Young ◽  
Deborah H. Strickland
Keyword(s):  
T Cell ◽  
B Cell ◽  
Plasma Cells ◽  
Effector Memory ◽  
High Dimensional ◽  
Cell Populations ◽  
Lymphoid Tissues ◽  
Murine Models ◽  
Follicular Helper ◽  
B Cell Subsets

Purpose and appropriate sample typesThis 19-parameter, 18-colour flow cytometry panel was designed and optimised to enable the comprehensive and simultaneous immunophenotyping of distinct T-cell and B-cell subsets within murine lymphoid tissues (Table 1). Cellular populations identified by employing this OMIP include 4 major subsets of B-cells (memory, activated, plasma cells and plasmablasts) and 7 major subsets of CD4+ T-cells (naïve, central memory, effector memory, helper, regulatory, follicular helper and follicular regulatory). Staining was performed on freshly isolated splenocytes from 21-day-old neonatal BALB/c mice, however due to the omission of mouse strain-specific markers, this OMIP can be implemented across a range of murine models where in-depth immunophenotyping of the diverse repertoire of T-cell and B-cell populations localised within lymphoid tissues is required.

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