BACKGROUND Mast cells and macrophages are tissue-resident immune cells frequently found in close proximity in barrier organs. Macrophages show high plasticity and microenvironmental factors, such as cytokines, can influence their phenotype. Mast cells are central in allergic reactions where allergens cause mast cell activation via antigen-specific IgE antibodies and the release of a multitude of inflammatory

BACKGROUND Anti-type 2 cytokine therapies represent promising interventions for chronic itch; however, their precise mechanisms in restoring nerve architecture and mitigating inflammation and pruritus remain incompletely understood. OBJECTIVES This study aimed to elucidate the mechanistic roles of IL-4, IL-13, and IL-31 in the pathophysiology of itch associated with type 2 inflammatory skin diseases

BACKGROUND Macrophages (Mphs) exhibit high heterogeneity and plasticity, which is essential for their multifaceted roles in host defense and tissue regeneration. Mast cells (MCs) respond rapidly to injury or infection by releasing intact secretory granules, thereby initiating and potentiating innate and adaptive immunity. OBJECTIVE Since MCs reside in close proximity to Mph in the skin, we decoded

Asthma is a complex and chronic respiratory condition that affects both adult and pediatric populations. Several asthma endotypes have been described; they include endotypes characterized by TH2 cell inflammation, response to viral infection, and exposure to air pollution. Recent evidence has revealed a novel endotype of pediatric asthma, termed the frequent exacerbator (FE) endotype, which is characterized

BACKGROUND Early infancy is marked by high susceptibility to severe viral respiratory infections and reduced protective antibody responses, making rapid development of local airway immunity essential. Despite this, the developmental dynamics of human airway B-cells and their interaction with airway epithelial cells (AECs) in early life remain poorly understood. OBJECTIVE To study the developmental

BACKGROUND In atopic dermatitis (AD), epidermal disease hallmarks are driven by a complex cutaneous inflammatory milieu that varies between patients. How these variable inflammatory signals affect cellular and molecular epidermal AD phenotypes is difficult to study in vivo. OBJECTIVE We aimed to unravel which AD-associated cytokines drive specific epidermal disease hallmarks. METHODS We utilized primary

BACKGROUND The nuclear factor kappa-light-chain enhancer of activated B cells (NF-κB) pathway is a key regulator of immune responses, cell survival, and proliferation. Dysregulation of this signaling pathway is implicated in various human diseases, including inborn errors of immunity. OBJECTIVE We describe the clinical heterogeneity in 16 patients from 4 unrelated families with missense variants in

BACKGROUND Immune cell metabolism and metabolic end-products influence the nature and magnitude of immune responses. Various autoimmune and inflammatory diseases are associated with dysregulated cellular metabolism. Intravenous immunoglobulin (IVIG), a therapeutic pooled normal IgG, is extensively used for the immunotherapy of a wide-range of autoimmune and inflammatory diseases. Although several cellular

BACKGROUND The infant nasal microbiota closely mediates the risks of developing childhood respiratory diseases. However, the primary sources of these early residing bacteria remain largely unknown, preventing the development of microbiome strategies for disease prevention. OBJECTIVE Identify the primary maternal source of bacteria found in the early infant nasal microbiome. METHODS We conducted a birth

BACKGROUND Viral infections and type 2 immune responses perpetuate airway epithelial barrier dysfunction and inflammation, leading to the development and progression of asthma. The synthetic cannabinoid WIN55,212-2 displays anti-inflammatory properties by acting on different immune system cells. OBJECTIVES To investigate the capacity of WIN55,212-2 to restore bronchial epithelial barrier function in

BACKGROUND Pulmonary involvement (repeated lung infections, lung parenchymal inflammation, scarring, and malignancies) is frequent in patients with inborn errors of immunity (IEI) and accounts for a significant proportion of the disease burden. Allogeneic hematopoietic stem cell transplantation (allo-HSCT) can cure most severe IEI. The indications for allo-HSCT have recently been extended to adults

BACKGROUND A large proportion of patients with common variable immunodeficiency (CVID) have autoimmune and inflammatory manifestations characterized by chronic T-cell- and monocyte/macrophage activation of unknown etiology. The tryptophan-kynurenine pathway has previously been linked to immune activation involving T cells and monocytes/macrophages, as well as with gut microbial dysbiosis in some inflammatory

BACKGROUND Lymphocytic variant hypereosinophilic syndrome (LHES) is a rare disorder characterized by hypereosinophilia, the presence of phenotypically aberrant populations of TH2 lymphocytes, and varied clinical manifestations. Although disease pathogenesis has historically been attributed to IL-5-driven hypereosinophilia, response to eosinophil-lowering biologics is not universal, suggesting a more

BACKGROUND Although clinical trials have demonstrated both the efficacy and safety of dupilumab, its impact on dendritic cells (DCs) remains unclear. TIM-3 has emerged as crucial regulators of immune responses in various inflammatory diseases. Understanding the interplay between TIM-3 and the type 2 inflammatory response in atopic dermatitis (AD) could provide valuable insights into the mechanisms

In January 2025, the American College of Gastroenterology (ACG) published updated guidelines on the diagnosis and management of eosinophilic esophagitis (EoE). These new guidelines incorporated updated information on the pathophysiology, risk factors, natural history, and treatment of EoE. As these guidelines were primarily intended for practicing gastroenterologists, this Paradigm and Perspectives

BACKGROUND Type I interferonopathy is characterized by aberrant upregulation of type I interferon signaling. The mRNA interferon signature is a useful marker for activation of the interferon pathway and for diagnosis of type I interferonopathy; however, early diagnosis is challenging. OBJECTIVE This study sought to identify the proteomic interferon signature in dried blood spot (DBS) samples. The aim

BACKGROUND During the COVID-19 pandemic, many individuals developed persistent symptoms after COVID-19. There is limited data on these long-term effects in the primary immunodeficiency (PID) community. OBJECTIVE This study aimed to understand long-term symptoms post-COVID-19 in PID patients, focusing on prevalence, risk factors, viral persistence and the impact of COVID-19 on their health-related quality

BACKGROUND IgE binding to linear peptides from the N-terminal region of Ara h 2 (epitope 1) is associated with the achievement of sustained unresponsiveness (SU) in young children receiving oral immunotherapy (OIT) and may be important for cross-reactivity between peanuts and tree nuts. This region is also part of the binding site for neutralizing IgG monoclonal antibodies associated with SU following

BACKGROUND Childhood asthma has been linked to distinct metabolomic profiles. OBJECTIVE We sought to identify phenotypes (metabotypes) in children with moderate to severe asthma through integrative fecal and serum metabolome analysis. METHODS Children from the Systems Pharmacology Approach to Uncontrolled Pediatric Asthma cohort with Global Initiative for Asthma treatment step 3 or higher were recruited

Emerging evidence reveals significant epidemiologic, genetic, and immunologic connections between atopic dermatitis, vitiligo, and alopecia areata, challenging previously established notions of their distinct pathogenic and molecular signatures. Exploring these commonalities not only enhances our understanding of each disease's pathogenesis, but also supports the development of unified treatment strategies

Climate change is imposing a profound effect on health conditions triggered by environmental exposures. Climate change has affected aeroallergens in numerous ways, including: (1) changes in the vegetation microbiome distribution, (2) increases in C4 grasses globally, (3) increased occurrence of acute weather events, (4) increases in ambient temperature that amplify fungal spore concentration and pollen

Birth cohorts have identified modifiable risk factors for asthma and respiratory health in children and adults, demonstrating the important role and pathways through which early-life events influence not only child outcomes but also adult health, disease, and mortality. This focused literature update from 2021 to 2024 summarizes birth cohort studies across the life-span that contribute to our understanding

BACKGROUND Asthma morbidity significantly affects children of all racial backgrounds; however, Black children experience a greater disease burden than children from other racial groups. Despite the known influence of air pollution on asthma outcomes, its role in the efficacy of asthma treatments remains underexplored. OBJECTIVE We sought to examine how exposure to particulate matter <2.5 μm (PM2.5)

BACKGROUND Sublingual immunotherapy (SLIT) was recently shown to safely induce desensitization and remission of peanut allergy in 1- to 4-year-old children. OBJECTIVE Basophil activation has been shown to be suppressed in allergen-specific immunotherapy. We aimed to evaluate the timing of basophil suppression during peanut SLIT and its impact on clinical outcomes. METHODS A total of 50 children with

BACKGROUND Chronic obstructive pulmonary disease (COPD) involves both local and systemic neutrophilic inflammation, with dysregulation in blood neutrophil numbers, frequencies, and functions. OBJECTIVE We sought to characterize the transcriptional and epigenetic profiles of circulating neutrophils in patients with COPD and explore correlations with neutrophil dysfunction and clinical disease parameters

The birth cohort study design is an essential epidemiologic tool for investigating the developmental origins of health and disease. Birth cohorts have greatly improved the etiologic understanding of asthma and allergic diseases, setting the stage for advancements in translational interventions. Increasingly, investigators leverage data repositories that have been compiled and maintained independently

Place-based measures of environmental exposures, climate, neighborhood characteristics, housing, and other social determinants of health are powerful predictors of health outcomes, including asthma. In addition, social determinants of health are likely causes of the persistent racial and ethnic disparities in asthma prevalence and morbidity. The objectives of this commentary are to (1) provide an overview

BACKGROUND Although phenotypic features have traditionally guided treatment in chronic rhinosinusitis, recent research has favored categorization on the basis of inflammatory endotype. However, the impact of endotypic differeces on clinical outcomes remains largely unknown. OBJECTIVE We sought to compare disease trajectory, primarily time-to-polyp recurrence, between chronic rhinosinusitis with nasal

BACKGROUND Biallelic loss-of-function mutations in the lipopolysaccharide-responsive and beige-like anchor (LRBA) gene lead to a severe syndrome of early-onset immune dysregulation called LRBA deficiency. Monoallelic CTLA4 mutations lead to a similar phenotype. In both conditions, cytotoxic T lymphocyte-associated protein 4 (CTLA-4) levels are significantly decreased. In previously reported cases of

The current understanding of chronic spontaneous urticaria (CSU) suggests that a complex network of inflammatory pathways is involved in its pathogenesis. Recent development highlighted autoimmunity as one of the key pathogenic mechanisms of CSU. Two endotypes, type I autoallergic (associated with IgE antibodies against autoantigens) and type IIb autoimmune (mediated by IgG autoantibodies against IgE

Chimeric antigen receptor (CAR) T and natural killer (NK) cell therapies represent a promising strategy for the treatment of cancers and other chronic diseases. Engineered CAR constructs endow immune cells with the ability to target desired antigens with high specificity, allowing for directed responses to antigen-expressing cells. CAR T and NK cells have shown marked success in the treatment of hematologic

Our understanding of the complement system continues to grow beyond that of a liver-derived systemically operative mechanism of pathogen clearance to a central orchestrator of single-cell behavior and tissue biology. These expanded activities reflect the extrahepatic and local production of complement by many, if not most, cells, and the unexpected recent finding that complement also serves important

BACKGROUND Mucosal immune responses and epithelial barrier function are key emerging determinants of susceptibility to wheezing illnesses in early life. OBJECTIVE We sought to investigate the association between nasal transcriptome in healthy infants and the subsequent incidence of recurrent wheeze. METHODS In a population-derived prebirth cohort study, whole-transcriptome sequencing was performed

BACKGROUND Early childhood wheeze is characterized by heterogeneous trajectories having differential associations with later-life asthma development. OBJECTIVE We sought to determine how early-life wheeze trajectories impact later life asthma gene expression. METHODS The Children's Respiratory Environmental Workgroup is a collective of 12 birth cohorts, 7 of which conducted an additional visit with

BACKGROUND TNF-α is an important proinflammatory cytokine, but its neutralization in the management of inflammatory skin disorders like psoriasis may trigger eczematous skin lesions as an adverse reaction. OBJECTIVES This study aimed to elucidate whether TNF-α may protect from skin inflammation and to identify in detail the underlying mechanisms. METHODS Wild-type, TNF-α-deficient, thymic stromal lymphopoietin

BACKGROUND Gut microbiota has been associated with health and susceptibility to childhood diseases, including asthma and allergies. However, the genomic factors contributing to interindividual variations in gut microbiota remain poorly understood. OBJECTIVE We sought to integrate host genomics with early-life exposures to investigate main and interaction effects on gut microbiota during the first year

BACKGROUND Novel specific therapy in chronic obstructive pulmonary disease (COPD) will require accessible targets for endotyping to identify responsive patients. It is therefore of interest that IL-26 in the bronchoalveolar space is enhanced and associates with bronchoalveolar pathology among long-term smokers (LTS) with and without COPD. OBJECTIVE We determined whether IL-26 in the nasal cavity can

BACKGROUND To support heterologous vaccine regimens, periodic severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) revaccination requires immunogenicity and safety data for adjuvanted protein-based vaccines following prior mRNA doses. OBJECTIVE We sought to assess noninferiority of neutralizing antibody (nAb) titers following a second dose versus a first dose (in a prior study) of an SARS-CoV-2

The US Food and Drug Administration (FDA) hosted a workshop on February 22, 2024, to discuss the status of biomarkers in drug development for allergic asthma and food allergy. The workshop provided a forum for open discussion among regulators, academicians, National Institutes of Health staff and industry to inform stakeholders of the requirements for the FDA to adopt a biomarker as a surrogate end

The field of genetic etiology of allergic diseases has advanced significantly in recent years. Shared risk loci reflect the contribution of genetic factors to the sequential development of allergic conditions across the atopic march, while unique risk loci provide opportunities to understand tissue specific manifestations of allergic disease. Most identified risk variants are noncoding, indicating

The management of chronic rhinosinusitis with nasal polyps (CRSwNP) can be challenging, particularly when standard treatments including intranasal corticosteroids and endoscopic sinus surgery do not result in adequate symptom control. CRSwNP is frequently characterized by a type 2 immune signature, and many patients have other comorbid type 2 conditions, including asthma. There are currently 3 biologic

Asthma is a heterogeneous disease with diverse underlying mechanisms contributing to disease susceptibility and progression. Asthma endotypes and phenotypes have emerged as critical frameworks to help understand the variation in disease presentation and response to therapies. Phenotypes are the observable characteristics or traits of an organism that are produced by the interaction of genotype and

BACKGROUND Mast cell (MC) activation plays a central role in the pathogenesis of chronic spontaneous urticaria (CSU). Mutations in MC receptors have been suggested as a potential mechanism underlying CSU. MRGPRX2 has been proposed to contribute to the pathogenesis of CSU. However, the relationship between mutations in MRGPRX2 and their impact on disease severity and receptor function remains poorly

Aspirin-exacerbated respiratory disease (AERD) is characterized by the clinical triad of chronic rhinosinusitis with nasal polyps, asthma, and a hypersensitivity to nonsteroidal anti-inflammatory drugs (NSAIDs). AERD is estimated to occur in as many as 15% of patients with chronic rhinosinusitis with nasal polyps and/or asthma. Uniquely, patients with AERD develop respiratory symptoms within 30 to

BACKGROUND IRF2BP2 is a transcription factor that plays an important role in regulating immune pathways, angiogenesis, apoptosis, and cell differentiation. Defects in this gene have been implicated in immunodeficiency. OBJECTIVES To deepen the understanding of the clinical implications of IRF2BP2 variants, we sought to clinically characterize and functionally test 34 individuals with IRF2BP2 variants