Epidemic thunderstorm asthma (ETSA) has historically been characterised around grass pollen in temperate Australia and Europe, whereas reports from northern China suggest an Artemisia-associated and potentially recurrent pattern. This systematic review synthesises primary evidence on the epidemiology, allergen profile, clinical features and early-warning systems of ETSA, comparing the Chinese and grass-pollen experiences. Following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) 2020 statement, PubMed, Web of Science, the China National Knowledge Infrastructure (CNKI) and Wanfang were searched to 30 June 2026, and reference lists were screened. Two reviewers independently selected studies, extracted data and assessed risk of bias with the Newcastle-Ottawa Scale and the Murad tool; certainty was rated using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach. Because of clinical and methodological heterogeneity, no meta-analysis was performed. Of 436 records identified and 333 screened after de-duplication, 54 primary studies were included (43 international and 11 Chinese, spanning Yulin, Hohhot, Chongqing, Lanzhou and Shenzhen). Three recurring observational patterns were identified. Chinese reports, especially from northern and north-western China, frequently described mugwort (Artemisia) sensitisation rather than ryegrass sensitisation; the proportion without a prior asthma diagnosis was high in both settings (approximately 40
Environmental pollution has emerged as one of the biggest threats to health in the contemporary world. Pollutants modify immune responses and may induce immunotoxicity. In this review, we describe the impact of significant environmental pollutants on the innate immune system, including ozone (O3), particulate matter (PM), diesel exhaust particles (DEPs) and cigarette smoke (CS), as well as emerging pollutants such as chemical contaminants, nanomaterials, and microplastics, with a particular focus on the regulatory mechanisms of innate lymphoid cells (ILCs). ILCs, tissue-resident lymphocytes without antigen-specific receptors, have been demonstrated to be essential regulators linking environmental detection and immunological responses. Studies indicate that environmental pollutants activate ILCs and alter the immune responses by compromising the epithelial barrier and triggering the release of alarmins, including interleukin (IL)-33, IL-25, and thymic stromal lymphopoietin (TSLP). Among ILCs, group 2 innate lymphoid cells (ILC2s) are highly sensitive to pollutant-induced epithelial signals and play a critical role in type 2 inflammation. Beyond canonical alarmin signaling, accumulating evidence indicates that environmental pollutants regulate ILC2 biology thereby contributing to immune dysregulation and inflammatory diseases. A better understanding of how environmental pollutants regulate ILC2 activation, plasticity, and functional adaptation will facilitate the development of more precise preventive and therapeutic strategies for pollution-associated diseases.
Atopic dermatitis (AD) is a heterogeneous inflammatory skin disorder characterized by recurrent eczematous lesions and persistent pruritus. Its pathogenesis involves epidermal barrier dysfunction, immune dysregulation, microbial dysbiosis, and altered neuroimmune signaling. Genetic defects in structural proteins, particularly filaggrin, and altered epidermal lipids increase allergen and microbial penetration, perpetuating itch, scratching, tissue injury, and inflammation. Molecular evidence further reveals AD endotypes beyond conventional clinical phenotypes, with heterogeneity in immune polarization, barrier dysfunction, microbial colonization, and pruritic pathways. This heterogeneity may underlie differences in clinical presentation and treatment response. Conventional treatments, including skin hydration, antihistamines, and topical anti-inflammatory agents, often provide incomplete or transient control. Mechanism-based therapies targeting IL-4/IL-13, OX40/OX40L, JAK, and PDE4, together with AhR agonists, have broadened treatment options. However, efficacy must be balanced against treatment-specific risks. Biologics require monitoring for ocular and injection-site reactions, whereas systemic JAK inhibitors require monitoring for infections and laboratory abnormalities and carry regulatory class warnings regarding major adverse cardiovascular events, venous thromboembolism, and malignancy; however, these warnings are largely extrapolated from studies in older patients with rheumatoid arthritis, and the magnitude of these risks in patients with AD remains uncertain. Long-term safety and real-world evidence remain limited for several emerging therapies. This review synthesizes current knowledge of barrier dysfunction, immune heterogeneity, molecular endotypes, microbiome imbalance, neuroimmune signaling, and mechanism-based therapies. Integrating clinical phenotypes with molecular endotypes, predictive biomarkers, efficacy, and individualized safety assessment may enable more precise treatment selection and durable disease control.
Common variable immunodeficiency (CVID) is the most prevalent symptomatic primary immunodeficiency, affecting approximately 1 in 25 000–50 000 individuals. Although classically characterized by hypogammaglobulinemia and recurrent bacterial infections, over 50
The gut microbiota plays a crucial role in human health and is increasingly recognized as a potential therapeutic target for various diseases. Current standard-of-care treatments for autoimmune diseases often include immunosuppressive agents aimed at controlling immune activation and limiting tissue injury rather than solely suppressing autoantibody production. However, systemic immunosuppression can be associated with dose- and duration-dependent adverse effects, underscoring the need to explore adjunctive and alternative therapeutic strategies. This review summarizes the putative mechanisms of action of seven commonly studied probiotic taxa: Lactobacillus, Bifidobacterium, Propionibacterium, butyrate-producing bacteria, yeasts, Enterococcus, and Bacillus. These taxa are presented as representative examples rather than an exhaustive list. The review further compares their commonalities and differences in immunomodulatory features across major autoimmune diseases, including systemic lupus erythematosus (SLE), Sjögren's syndrome (SS), and rheumatoid arthritis (RA). We further discuss evidence for potential synergy among probiotic combinations, contrast probiotic-based interventions with conventional immunosuppressive regimens in terms of their putative advantages and limitations, and examine the prospects for precision probiotic strategies alongside current challenges, including strain specificity, dosing and formulation, host heterogeneity, and reproducibility across cohorts. By integrating existing evidence, this review aims to inform the rational development of probiotic-based interventions for autoimmune diseases and provide a framework for future clinical and translational research.
Glycosylation is a critical post-translational modification that regulates protein folding, stability, and cellular communication. Among glycan modifications, fucosylation, catalyzed by fucosyltransferases (FUTs), plays important roles in immune regulation, epithelial homeostasis, and host-pathogen interactions. Increasing evidence suggests that dysregulated fucosylation contributes to chronic inflammatory airway diseases, including asthma. Asthma is characterized by chronic airway inflammation, epithelial barrier dysfunction, mucus hypersecretion, and airway remodeling, processes that are increasingly associated with altered glycosylation patterns. Recent studies indicate that specific FUT isoforms regulate epithelial integrity, mucin glycosylation, immune-cell recruitment, and inflammatory signaling in asthma. Emerging evidence also suggests that FUT-mediated fucosylation may contribute to airway remodeling and cellular senescence; however, direct evidence for these mechanisms in asthma remains limited, and many insights are derived from related respiratory diseases and experimental models. This review summarizes current knowledge of the FUT family and critically evaluates the evidence linking aberrant fucosylation to asthma pathogenesis. We discuss the roles of FUTs in epithelial dysfunction, mucus secretion, immune regulation, airway remodeling, and cellular senescence, while distinguishing established asthma-specific findings from emerging mechanistic hypotheses. Finally, we highlight current challenges, future research directions, and the potential of FUT-targeted strategies for biomarker discovery and precision therapies in asthma.
Autoimmune hepatitis (AIH) is an idiopathic autoimmune disorder characterized by chronic liver inflammation that, if untreated, can lead to liver fibrosis and cirrhosis, hepatic failure, and death. Current treatment options for this potentially life-threatening disorder include either high-dose immunosuppressants or liver transplantation (for late-stage patients). However, these options are risky and can lead to long-term complications. Therefore, there is an urgent need to develop novel treatment strategies for AIH. Therapeutic approaches based on mesenchymal stem/stromal cells (MSCs) and their derived extracellular vesicles (EVs) have emerged as a viable treatment option for AIH because of their potent immunomodulatory and anti-inflammatory properties. This review outlines the recent developments in the use of these therapies for the treatment of AIH. The use of EVs as vehicles for the delivery of therapeutic drugs or miRNAs is also discussed. In addition, we discuss the various efforts that have been made to improve the efficacy of such therapies, including their genetic modification and combination with anti-inflammatory drugs. Finally, we proposed several directions for future research aimed at developing MSCs and MSC-derived EVs for clinical applications.
Hereditary angioedema (HAE) is a rare genetic disease characterized by unpredictable, painful cutaneous and/or subcutaneous swelling attacks; laryngeal attacks can be fatal. For many patients, long-term prophylaxis (LTP) is critical for disease control and quality of life. Lanadelumab, a plasma kallikrein inhibitor, was approved for HAE LTP for adults and adolescents in 2018 and for children aged ≥ 2 years in 2023; it is currently one of the guideline-recommended, first-line LTP options. By integrating 7 years of cumulative clinical trial and real-world data, this narrative review summarizes lanadelumab long-term effectiveness and safety in adult, adolescent, and pediatric HAE populations. Outcomes in 41 peer-reviewed publications were evaluated, including 5 clinical trials involving 262 lanadelumab-treated patients and 28 real-world studies comprising 700 patients. Across clinical trials, lanadelumab reduced attack rates by up to 100
The OX40-OX40L co-stimulatory pathway has emerged as an important regulator of T-cell persistence and immune memory. While traditionally associated with type 2 inflammation, its role extends across multiple barrier tissues, including the skin and respiratory mucosa, where it integrates epithelial signals with adaptive immune responses. To provide a comprehensive and integrative overview of the OX40-OX40L axis as a shared driver of immune persistence across skin and airway inflammatory diseases and to discuss its therapeutic implications. A narrative review was conducted based on a focused literature search of PubMed, Scopus, and Web of Science up to February 2026. Experimental, translational, and clinical studies addressing OX40-OX40L biology and therapeutic targeting were included. OX40 signaling acts as a late co-stimulatory pathway that sustains effector T-cell survival, promotes tissue-resident memory T-cell formation, and modulates regulatory T-cell function. In barrier tissues, epithelial-derived alarmins such as TSLP and IL-33 induce OX40L expression on antigen-presenting cells, reinforcing type 2-polarized immune responses. This axis contributes to chronic inflammation in atopic dermatitis, asthma, allergic rhinitis, and nasal polyposis, supporting the concept of shared mechanisms of immune persistence across type 2 inflammatory diseases. Beyond type 2 immunity, OX40-OX40L signaling also participates in Th1-, Th17-, and Th22-mediated responses, as well as in autoimmune, fibrosing, and lymphoproliferative disorders. Therapeutic targeting of this pathway, particularly with monoclonal antibodies such as amlitelimab, has demonstrated clinically meaningful efficacy and suggests potential for durable disease modification. The OX40-OX40L axis represents an important immunological pathway linking epithelial activation to adaptive immune memory across barrier tissues. Its role in sustaining immune persistence provides a conceptual framework for understanding chronic inflammatory diseases and supports continued investigation of therapies targeting upstream co-stimulatory pathways.
Emerging infectious threats continually challenge the adaptability of the human immune system. Inborn errors of immunity (IEIs) provide a unique framework to dissect host-pathogen interactions, revealing how single-gene defects uncover critical pathways in antifungal defence. This review offers an overview of fungal immunity through the lens of IEIs, and integrates recent advances in innate fungal recognition, neutrophil and mononuclear phagocyte effector mechanisms, CARD9/NF-kB signalling, IL-17/IL-23 and IL-12/IFN-gamma cytokine axes, and transcription-factor defects that shape susceptibility to Candida, Aspergillus, Pneumocystis, Cryptococcus, dimorphic fungi and other moulds. We also discuss acquired phenocopies mediated by anti-cytokine autoantibodies, translate these mechanisms into clinical red flags and diagnostic algorithms, and discuss potential therapeutic strategies. Finally, we highlight how genetically defined IEIs can be used to study fungal-bacterial, fungal-mycobacterial and fungal-viral co-infections, revealing the hierarchy and plasticity of host defence in health and disease.
Bradykinin is a nonapeptide of the kinin family with vasoactive and proinflammatory activities. While generation of kinins is mainly driven by activation of the contact system and plasma or tissue kallikreins, additional independent cascades contribute to their formation. Kinins mediate their effects through the constitutively expressed bradykinin B2 receptor and the inducible bradykinin B1 receptor. Bradykinin is the most studied kinin peptide mainly due to its potential role in the vascular system and exerts its effects mainly via the bradykinin B2 receptor. Kinins have been implicated in the pathogenesis of multiple types of angioedema as well as of various conditions, such as allergic mast cell-mediated skin diseases, cardiovascular and respiratory pathologies. This review summarizes our current knowledge of the biology, regulation, and functions of kinins and their receptors as well the emerging evidence on the various mechanisms involved in bradykinin formation and their relevance in disease pathogenesis. The review focuses on the clinical evidence on the roles of bradykinin and of the bradykinin B2 receptor in various conditions, and the potential to develop novel strategies targeting the bradykinin B2 receptor for management of bradykinin-mediated diseases.
Chronic urticaria is a common skin disorder that substantially affects both daily functioning and quality of life. Among its subtypes, chronic inducible urticaria often presents with greater therapeutic challenges than chronic spontaneous urticaria. A comprehensive review of the available evidence indicates that β-blockers may offer a rapid-acting, well-tolerated, and effective treatment option for patients with specific subtypes of chronic inducible urticaria specifically cholinergic urticaria, adrenergic urticaria, and the aquagenic continuum. This approach introduces a readily available, non-parenteral, and cost-efficient therapeutic alternative that could also yield novel insights into the underlying pathophysiology of urticaria. In addition, this manuscript underscores the need to update current clinical guidelines by: (1) recognizing adrenergic urticaria as a distinct chronic inducible urticaria subtype; (2) broadening the conceptual framework for aquagenic-induced symptoms; and (3) standardizing intradermal test concentrations for adrenergic and cholinergic urticaria.
Reactive infectious mucocutaneous eruption (RIME) is increasingly recognized as a pediatric syndrome in which severe mucositis follows a recent infection and cutaneous involvement is usually limited. Although Mycoplasma pneumoniae remains the prototype trigger, influenza, SARS-CoV-2, adenovirus, respiratory syncytial virus, and other respiratory pathogens can produce a similar clinical phenotype. This narrative review summarizes pediatric RIME/MIRM literature and selected adult or comparator-disease evidence when direct pediatric data are unavailable, explicitly distinguishing direct RIME evidence from extrapolated mechanisms. This review synthesizes current evidence on the immunopathogenesis of RIME in children, with emphasis on how pathogen-specific factors intersect with innate and adaptive immune pathways to drive mucosal injury. We discuss the central roles of epithelial sensing, inflammasome activation, cytokine amplification, neutrophil recruitment, and T-cell polarization, and we relate these mechanisms to the severe oral, ocular, and anogenital disease that often defines pediatric presentations. We also integrate emerging proteomic data showing recurring molecular programs, including acute-phase and complement activation, neutrophil-associated epithelial injury, and interferon-inducible antiviral responses. In addition, we review the possible contribution of genetic susceptibility, especially variation in innate immune sensors and cytokine signaling pathways, to disease severity and recurrence. Finally, we address the main diagnostic challenges, histopathologic and imaging findings, differential diagnosis from Stevens-Johnson syndrome, erythema multiforme, and Kawasaki disease, and the implications of these insights for risk stratification and treatment. Taken together, current evidence supports RIME as a pathogen-triggered, mucosa-predominant inflammatory syndrome in which exaggerated host responses, rather than pathogen presence alone, shape the clinical phenotype.
Autoimmune diseases are characterized by the immune system's breakdown of self-tolerance, and manifest as either organ-specific or systemic conditions. Within the target tissues of diverse autoimmune diseases, tertiary lymphoid structures (TLSs) emerge under persistent inflammatory conditions. These pathological, ectopic lymphoid formations serve as sites for sustained antigen presentation, affinity maturation of antibodies, and proliferation /differentiation of B cells, thereby exacerbating local immune-mediated damage. Given their functional significance, TLSs represent promising candidates as diagnostic biomarkers and novel therapeutic targets for autoimmune pathologies. This review synthesizes the current knowledge on the pathological relevance of TLSs, the mechanisms driving their formation and the therapeutic targeting potential, aiming to deepen the understanding of how TLSs influence the immune microenvironment in autoimmune disease pathology.
The incidence of acute-onset autoimmune hepatitis (A-AIH) is increasing, yet diagnosis remains challenging, especially in patients with recent hepatotoxic drug exposure. The clinical presentations of A-AIH and drug-induced autoimmune-like hepatitis (DI-ALH) at onset are often indistinguishable, complicating timely diagnosis. We conducted a three-center retrospective study in China, screening patients with acute liver injury, hepatotoxic drug exposure, and autoimmune features. Patients were ultimately classified as DI-ALH if they achieved sustained remission after culprit drug cessation, or as A-AIH if they relapsed. We compared baseline demographics, laboratory indices, immunological profiles, liver histology, and established AIH diagnostic criteria. We developed and independently validated a multivariable logistic regression model to improve discrimination between A-AIH and DI-ALH. Of 458 patients screened, 238 met inclusion criteria and constituted the final cohort (94 A-AIH and 144 DI-ALH). Compared to DI-ALH, A-AIH showed significantly higher IgG levels, lower platelet counts, and higher autoantibody titers. Histologically, A-AIH exhibited more severe portal inflammation, interface hepatitis, fibrosis, and rosette formation. The discriminatory capacity of the 2022 and 2008 histological criteria was limited and comparable (AUC 0.62 vs. 0.59, p = 0.616). The Dx-AID score, incorporating platelet count, IgG, autoantibodies, and histological features, achieved high diagnostic accuracy in both the derivation cohort (AUC 0.84, 95
Data on neuro-Behçet’s disease in North Africa remain limited and fragmented. We conducted a systematic review and meta-analysis to estimate the frequency of neurologic involvement in North African patients with Behçet’s disease and to summarize the main clinical, cerebrospinal fluid, and imaging characteristics. PubMed, Scopus, and Web of Science databases were searched for studies reporting neuro-Behçet’s disease in North Africa. Proportions were pooled using a random-effects meta-analysis model to estimate overall pooled proportions (OPP). Heterogeneity was assessed using I2 statistics. The review protocol was registered in PROSPERO (CRD420261303759). Thirteen studies were included. Among 4262 patients with Behçet’s disease, the pooled proportion of Neuro-Behçet’s disease was 18.54
Over recent decades, the prevalence of allergic diseases has risen steadily, particularly among children, making these conditions a major global public health concern. Increasing evidence suggests that, in addition to genetic factors, gut microbiota dysbiosis is an important contributor to the development and progression of allergic diseases. The gut microbiota plays a critical role in host metabolism, maintenance of mucosal barrier integrity, and regulation of immune homeostasis, and is especially closely linked to immune system development and the establishment of immune tolerance in early life. Abnormalities in the composition and function of the gut microbiota may promote allergic susceptibility through multiple immunoregulatory pathways and contribute to the onset and progression of atopic dermatitis, allergic rhinitis, asthma, and other allergic diseases. This review focuses on the relationship between early-life gut microbiota and allergic diseases, summarizes the underlying immunoregulatory mechanisms, and discusses progress in microbiota-targeted interventions, with the aim of providing a reference for early prevention and precision intervention in allergic diseases.
Obesity-related asthma is a major clinical challenge defined by its unique pathology and resistance to corticosteroids. Here, we reframe this disease through the lens of tissue-specific "maladaptive plasticity" of group 2 innate lymphoid cells (ILC2s). We propose a central dichotomy: in the obese lung, mechanical transduction synergizes with metabolic inflammation to induce a HIF-1α-mediated glycolytic shift in ILC2s. Conversely, in visceral adipose tissue (VAT), chronic metabolic stress drives ILC2 functional exhaustion, suppressing cytokine secretion. This pulmonary glycolytic shift fuels acetyl-CoA accumulation and subsequent epigenetic remodeling, which locks ILC2s into a pathogenic ILC1/ILC3-like phenotype, thereby driving the non-Th2 inflammation characteristic of obesity-related asthma. Furthermore, we describe how systemic metabolic stress propagates through the "adipose-pulmonary" and "gut-pulmonary" axes, which includes neutrophil extracellular traps (NETs) and glucocorticoid receptor isoform imbalances. Collectively, these pathological changes establish a refractory network of corticosteroid resistance, a primary factor contributing to treatment failure in obesity-related asthma. Based on these findings, we propose a novel therapeutic framework termed "Metabolic Resuscitation". This strategy shifts the focus from conventional immunosuppression to restoring cellular homeostasis by targeting key metabolic checkpoints and epigenetic drivers. This review provides a new mechanistic framework for understanding obesity-related asthma and offers a rationale for developing therapies to reverse treatment resistance.
Alopecia areata (AA) is a common autoimmune, non-scarring hair loss disorder with substantial clinical heterogeneity and psychosocial burden. Although recent therapeutic advances, particularly Janus kinase (JAK) inhibitors, have transformed management, the pathogenic mechanisms underlying disease initiation, progression, and relapse remain incompletely understood. Current evidence supports the collapse of hair follicle immune privilege as a central event in AA, followed by the activation of cytotoxic T-cell–dominant responses and amplification through IFN-γ/IL-15-driven inflammatory circuits. However, the contributions of innate immune populations, neuroimmune stress pathways, and hair follicle resident compartments to disease heterogeneity are still being clarified. In parallel, experimental models have proven essential for mechanistic investigation and therapeutic development. Classical C3H/HeJ mice, humanized models, and genetically engineered systems provide critical insights into immune-mediated follicular injury and serve as valuable platforms for drug screening. Furthermore, in vitro and ex vivo models, including hair follicle organ cultures, scalp explants, and novel bioengineered platforms, facilitate the detailed investigation of early pathological events and their underlying mechanisms. Yet, no single model fully captures the entire disease continuum. This review synthesizes the current understanding of AA immunopathology and systematically evaluates available experimental platforms with an emphasis on their biological fidelity, strengths, limitations, and translational applications. By integrating pathogenic mechanisms with model selection, this review aims to provide a practical framework for future AA research and therapeutic innovation.
