CD4+ memory/effector T cells play a central role in orchestrating the rapid and robust immune responses upon re-encounter with specific Ags. However, the immunologic mechanism(s) underlying these responses are still not fully understood. To investigate this, we generated an allergen (major house dust mite allergen, Blo t 5)-specific murine Th2 cell line that secreted IL-4, IL-5, IL-10, and IL-13, but not IL-9 or TNF-α, upon activation by the cognate Ag. These cells also exhibited CD44highCD62L− and CD127+ (IL-7Rα+) phenotypes, which are characteristics of memory/effector T cells. Experiments involving adoptive transfer of this Th2 cell line in mice, followed by three intranasal challenges with Blo t 5, induced a dexamethasone-sensitive eosinophilic airway inflammation. This was accompanied by elevation of Th2 cytokines and CC- and CXC-motif chemokines, as well as recruitment of lymphocytes and polymorphic mononuclear cells into the lungs. Moreover, Blo t 5-specific IgE was detected 4 d after the last intranasal challenge, whereas elevation of Blo t 5-specific IgG1 was found at week two. Finally, pulmonary delivery of the pVAX–IL-35 DNA construct effectively downregulated Blo t 5-specific allergic airway inflammation, and i.m. injection of pVAX–IL-35 led to long-lasting suppression of circulating Blo t 5-specific and total IgE. This model provides a robust research tool to elucidate the immunopathogenic role of memory/effector Th2 cells in allergic airway inflammation. Our results suggested that IL-35 could be a potential therapeutic target for allergic asthma through its attenuating effects on allergen-specific CD4+ memory/effector Th2 cell-mediated airway inflammation.

Evidence is accumulating that the establishment of the gut microbiome in early life influences the development of atopic eczema. In this longitudinal study, we used integrated multi-omics analyses to infer functional mechanisms by which the microbiome modulates atopic eczema risk. We measured the functionality of the gut microbiome and metabolome of 63 infants between ages 3 weeks and 12 months with well-defined eczema cases and controls in a sub-cohort from the Growing Up in Singapore Toward healthy Outcomes (GUSTO) mother-offspring cohort. At 3 weeks, the microbiome and metabolome of allergen-sensitized atopic eczema infants were characterized by an enrichment of Escherichia coli and Klebsiella pneumoniae , associated with increased stool D-glucose concentration and increased gene expression of associated virulence factors. A delayed colonization by beneficial Bacteroides fragilis and subsequent delayed accumulation of butyrate and propionate producers after 3 months was also observed. Here, we describe an aberrant developmental trajectory of the gut microbiome and stool metabolome in allergen sensitized atopic eczema infants. The infographic describes an impaired developmental trajectory of the gut microbiome and metabolome in allergen-sensitized atopic eczema (AE) infants and infer its contribution in modulating allergy risk in the Singaporean mother-offspring GUSTO cohort. The key microbial signature of AE is characterized by (1) an enrichment of Escherichia coli and Klebsiella pneumoniae which are associated with accumulation of pre-glycolysis intermediates (D-glucose) via the trehalose metabolic pathway, increased gene expression of associated virulence factors (invasin, adhesin, flagellin and lipopolysaccharides) by utilizing ATP from oxidative phosphorylation and delayed production of butyrate and propionate, (2) depletion of Bacteroides fragilis which resulted in lower expression of immunostimulatory bacterial cell envelope structure and folate (vitamin B9) biosynthesis pathway, and (3) accompanied depletion of bacterial groups with the ability to derive butyrate and propionate through direct or indirect pathways which collectively resulted in reduced glycolysis, butyrate and propionate biosynthesis.

Food allergy rates in Singapore are low despite delayed introduction of allergenic foods. Early introduction of allergenic foods may thus not be necessary in populations in which overall food allergy prevalence is low, and thus infant feeding recommendations should be carefully tailored to individual populations.

No abstract

There is a striking age-related disparity in the prevalence and severity of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-induced coronavirus disease 2019 infections, which might be explained by age-dependent immunological mechanisms. These include age-related physiological differences in immunological responses, cross-neutralizing antibodies, and differences in levels and binding affinity of angiotensin-converting enzyme 2, the SARS-CoV-2 target receptor; antibody-dependent enhancement in adults manifesting with an overexuberant systemic inflammation in response to infection; and the increased likelihood of comorbidities in adults and the elderly. Emerging immunological phenomena such as Pediatric Multi-System Inflammatory Disorder Temporally associated with SARS-CoV-2 or Multisystem Inflammatory Syndrome in Children are now being observed, though the underlying mechanisms are still unclear. Understanding the mechanisms through which pediatric patients are protected from severe novel coronaviruses infections will provide critical clues to the pathophysiology of coronavirus disease 2019 infection and inform future therapeutic and prophylactic interventions. Asymptomatic carriage in children may have major public health implications, which will have an impact on social and health care policies on screening and isolation practices, school reopening, and safe distancing requirements in the community.

Atopic dermatitis (AD) is one of the most common chronic inflammatory skin disorders, which often develops in early infancy and may persist into adulthood. 1 The pathogenesis of AD has yet to be fully elucidated, but it is considered to be complex and multifactorial, attributed to an interplay of genetics, immune, and environmental factors. 1,2 The International Study of Asthma and Allergies in Childhood (ISAAC) Phase 3 indicated the Asia Pacific region as an area of increasing AD prevalence. 3 However, the epidemiology of AD is highly variable worldwide and most of the published literature has so far focused mainly on Western populations. The risk factors contributing to the ethnic and geographical differences in AD are also not well established. Recent studies have shown variability in the immuno-phenotypes of AD among different ethnic groups and populations. These differences may in turn affect responses to treatment which are tailored mainly to a specific immuno-phenotype (T-helper type 2 (Th2) dominant). This review therefore seeks to collate existing literature on the prevalence of AD internationally; highlighting differences, if any, in the clinical and immuno-phenotypes of AD between different ethnicities and discusses possible factors accounting for the observed differences.

Background: Healthy gut microflora is essential for oral tolerance and immunity. A promising approach to preventing allergic diseases in genetically at-risk infants is to introduce administration of probiotics early in life when their immune system is still relatively immature. Objective: In this follow-up study, we aim to determine if early-life supplementation with strains of probiotics has any long-term effect on allergic outcomes. Methods: We analyzed the charts and electronic databases of the PROMPT (Probiotics in Milk for the Prevention of Atopy Trial) study cohort. This cohort consisted of 253 infants at risk for allergy who were administered cow's milk supplemented with or without probiotics from the first day of life to the age of 6 months. The cohort was then followed up until the children were 5 years old and clinical outcomes were assessed. Results: Of the 253 children recruited into the study, 220 (87%) completed the follow-up. At the age of 5 years, there were no significant differences between the groups in the proportion of children who had developed any asthma, allergic rhinitis, eczema, food allergy and sensitization to inhalant allergens. Similar growth rates were observed in both groups. Conclusions: The supplementation of probiotics in early childhood did not play a role in the prevention of allergic diseases. Clinical/Key Message: Early-life supplementation with probiotics did not change allergic outcomes at 5 years of age.

Background and Aim Gastrointestinal manifestations of the coronavirus disease 2019 (COVID‐19) pandemic may mimic irritable bowel syndrome (IBS), and social distancing measures may affect IBS patients negatively. We aimed to study the impact of COVID‐19 on respondents with self‐reported IBS. Methods We conducted an anonymized survey from May to June 2020 in 33 countries. Knowledge, attitudes, and practices on personal hygiene and social distancing as well as psychological impact of COVID‐19 were assessed. Statistical analysis was performed to determine differences in well‐being and compliance to social distancing measures between respondents with and without self‐reported IBS. Factors associated with improvement or worsening of IBS symptoms were evaluated. Results Out of 2704 respondents, 2024 (74.9%) did not have IBS, 305 (11.3%) had self‐reported IBS, and 374 (13.8%) did not know what IBS was. Self‐reported IBS respondents reported significantly worse emotional, social, and psychological well‐being compared with non‐IBS respondents and were less compliant to social distancing measures (28.2% vs 35.3%, P = 0.029); 61.6% reported no change, 26.6% reported improvement, and 11.8% reported worsening IBS symptoms. Higher proportion of respondents with no change in IBS symptoms were willing to practice social distancing indefinitely versus those who deteriorated (74.9% vs 51.4%, P = 0.016). In multivariate analysis, willingness to continue social distancing for another 2–3 weeks ( vs longer period) was significantly associated with higher odds of worsening IBS. Conclusion Our study showed that self‐reported IBS respondents had worse well‐being and compliance to social distancing measures than non‐IBS respondents. Future research will focus on occupational stress and dietary changes during COVID‐19 that may influence IBS.