Clinical Reviews in Allergy & Immunology最新文献

Atopic dermatitis (AD) is a chronic inflammatory skin disease with a complex relationship to allergens. While AD itself is not an allergic reaction and does not necessarily involve allergen sensitization, AD patients show higher rates of sensitization to food and inhalant allergens compared to the general population. Recent evidence refining the "dual allergen exposure hypothesis" demonstrates that early oral exposure to allergens through an intact gastrointestinal barrier typically promotes tolerance, while exposure through compromised skin or respiratory barriers often leads to sensitization. Therefore, the impaired skin barrier function in AD patients increases the risk of transcutaneous sensitization and may interfere with oral tolerance development. Interestingly, AD patients' sensitivity to contact allergens (such as metals and fragrances) is not necessarily higher than that of the general population, which may be related to the inherent properties of these allergens. Personalized allergen testing can help guide appropriate allergen avoidance and reintroduction strategies in AD management. The insights into optimal allergen exposure conditions have also expanded the potential applications of allergen-specific immunotherapy in preventing AD onset in high-risk populations and halting the atopic march.

Systemic lupus erythematosus (SLE) is an autoimmune disease that significantly increases the risk of cardiovascular diseases, particularly atherosclerosis (AS). Understanding the shared pathogenic mechanisms underlying SLE and AS is crucial for developing effective therapeutic strategies. Macrophages, as pivotal immune cells, play a critical role in the initiation and progression of atherosclerotic plaques within the context of SLE. This review delves into the molecular and cellular mechanisms governing macrophage activation and differentiation in response to SLE-related inflammatory mediators, highlighting their roles in lipid metabolism, plaque stability, and immune regulation. Additionally, we discussed the current treatment modalities for SLE and their impact on macrophage functionality, exploring these effects for atherosclerotic progression. By elucidating the intricate relationship between macrophages, SLE pathophysiology, and AS progression, this review underscores the need for a multidisciplinary approach in managing SLE and its cardiovascular complications, aiming to improve patient survival and quality of life through tailored therapeutic interventions addressing both autoimmune and cardiovascular pathologies.

Electronic cigarettes (EC) have emerged as a popular alternative to traditional tobacco products, but their impact on immune function has raised significant health concerns. This review explores the immunological effects of EC exposure, focusing on innate and adaptive immune responses. Electronic cigarette aerosol (ECA) induces widespread inflammation. These changes compromise immune cell function, impairing neutrophil chemotaxis, phagocytosis, and oxidative burst while increasing macrophage and dendritic cell recruitment and activation. ECA also disrupts epithelial barriers, increasing susceptibility to bacterial and viral infections. Studies show enhanced biofilm formation in bacteria such as Staphylococcus aureus and Streptococcus pneumoniae and impaired antiviral responses against pathogens like influenza A and SARS-CoV-2. Additionally, EC exposure modulates adaptive immunity, affecting T and B cell function and increasing systemic inflammatory markers. The long-term consequences of these immunological disruptions include heightened risks for chronic inflammatory diseases, respiratory infections, and potentially autoimmune conditions. The widespread adoption of EC, particularly among younger users, poses a growing public health challenge. As the popularity of vaping continues to rise, these immunological disruptions could result in increased healthcare burdens in the future, with higher rates of infections, chronic inflammatory diseases, and immune system-related disorders among those who begin using e-cigarettes at a young age. Understanding the full scope of EC-related health risks is essential for informing public health policies and protecting future generations from the potential long-term effects of vaping.

The intestinal microbiota is a complex community of organisms present in the human gastrointestinal tract, some of which can produce short-chain fatty acids (SCFAs) through the fermentation of dietary fiber. SCFAs play a major role in mediating the intestinal microbiota's regulation of host immunity and intestinal homeostasis. Respiratory syncytial virus (RSV) can cause an imbalance between anti-inflammatory and proinflammatory responses in the host. In addition, changes in SCFA levels and the structure of the intestinal microbiota have been observed after RSV infection. Therefore, there may be a link between SCFAs and RSV infection, and SCFAs are expected to be therapeutic targets for RSV infection.

Gastrointestinal Defects and Immunodeficiency Syndrome-1 (GIDID-1), caused by abnormalities in TTC7A, is an autosomal recessive disorder characterized by multiple gastrointestinal malformations and immune deficiencies, often accompanied by inflammatory bowel disease (IBD). This condition typically results in poor treatment outcomes and is usually fatal in early infancy. This paper examined the genetic abnormalities and clinical features of GIDID by analyzing data from three children and one fetus with gastrointestinal dysfunction and immune deficiency associated with TTC7A abnormalities at our hospital, and reviewed reported cases worldwide. Genetic analysis of the four patients identified eight novel variants in the TTC7A, five of which were likely pathogenic variants, while three were of uncertain significance. Including the cases reported in this paper and through a literature review, there were 89 known cases globally, involving 79 TTC7A variants. Patients typically presented with multiple gastrointestinal malformations, immune deficiencies, or IBD. Thus, genetic testing is recommended for patients with multiple gastrointestinal malformations and recurrent infections to determine if GIDID is due to TTC7A abnormalities. The syndrome generally has a poor prognosis, and this information is crucial for treatment planning, prenatal screening, and genetic counseling.

In recent years, epigenetic modifications have attracted significant attention due to their unique regulatory mechanisms and profound biological implications. Acting as a bridge between environmental stimuli and changes in gene activity, they reshape gene expression patterns, providing organisms with regulatory mechanisms to respond to environmental changes. A growing body of evidence indicates that epigenetic regulation plays a crucial role in the pathogenesis and progression of psoriasis. A deeper understanding of these epigenetic mechanisms not only helps unveil the molecular mechanisms underlying the initiation and progression of psoriasis but may also provide new insights into diagnostic and therapeutic strategies. Given the unique roles and significant contributions of various cell types involved in the process of psoriasis, a thorough analysis of specific epigenetic patterns in different cell types becomes a key entry point for elucidating the mechanisms of disease development. Although epigenetic modifications encompass multiple complex layers, this review will focus on histone modifications and DNA methylation, describing how they function in different cell types and subsequently impact the pathophysiological processes of psoriasis. Finally, we will summarize the current problems in research concerning histone modifications and DNA methylation in psoriasis and discuss the clinical application prospects and challenges of targeting epigenetic modifications as therapeutic strategies for psoriasis.

Exosomes, small extracellular vesicles secreted by various cell types, have emerged as key players in the pathophysiology of autoimmune diseases. These vesicles serve as mediators of intercellular communication, facilitating the transfer of bioactive molecules such as proteins, lipids, and nucleotide. In autoimmune diseases, exosomes have been implicated in modulating immune responses, oxidative stress, autophagy, gut microbes, and the cell cycle, contributing to disease initiation, progression, and immune dysregulation. Recent advancements in exosome isolation techniques and their molecular characterization have paved the way for exploring their clinical potential as biomarkers and therapeutic targets. This review focuses on the mechanisms by which exosomes influence autoimmune disease development and their potential clinical applications, particularly in diagnosis. The role of exosomes in autoimmune diseases, including systemic lupus erythematosus (SLE), rheumatoid arthritis (RA), type 1 diabetes mellitus (T1DM), inflammatory bowel disease (IBD), and Sjögren's syndrome (SS), is discussed in relation to their involvements in antigen presentation, T-cell activation, and the induction of inflammatory pathways. Additionally, exosome-based biomarkers offer promising non-invasive diagnostic tools for early diagnostic, disease monitoring, and therapeutic response assessment. However, challenges such as standardization of exosome isolation protocols and validation of their clinical significance remain. This review highlights the potential of exosomes as both diagnostic biomarkers and therapeutic targets in autoimmune diseases, emphasizing the need for further research to overcome current limitations and fully harness their clinical value.

Asthma is a complex disease with varied clinical manifestations resulting from the interaction between environmental and genetic factors. While chronic airway inflammation and hyperresponsiveness are central features, the etiology of asthma is multifaceted, leading to a diversity of phenotypes and endotypes. Although most research into the genetics of asthma focused on the analysis of single nucleotide polymorphisms (SNPs), studies highlight the importance of structural variations, such as copy number variations (CNVs), in the inheritance of complex characteristics, but their role has not yet been fully elucidated in asthma. In this context, an integrative review was conducted to identify the genes and pathways involved, the location, size, and classes of CNVs, as well as their contribution to asthma risk, severity, control, and response to treatment. As a result of the review, 16 articles were analyzed, from different types of observational studies, such as case-control, cohort studies and genotyped-proband or trios design, that have been carried out in populations from different countries, ethnicities, and ages. Chromosomes 12 and 17 were the most studied in three publications each. CNVs located on 12 chromosomes were associated with asthma, the majority being found on chromosome 6p and 17q, of the deletion type, encompassing 30 different coding-protein genes and one pseudogene region. Six genes with CNVs were identified as significant expression quantitative locus (eQTLs) with mean expression in asthma-related tissues, such as the lung and whole blood. The phenotypic variability of asthma may hinder the clinical application of these findings, but the research shows the importance of investigating these genetic variations as possible biomarkers in asthma patients.

The switch/sucrose non-fermentable (SWI/SNF) chromatin remodeling complexes (also referred to as BAF complexes) are composed of multiple subunits, which regulate the nucleosome translocation and chromatin accessibility. In recent years, significant advancements have been made in understanding mutated genes encoding subunits of the SWI/SNF complexes in cancer biology. Nevertheless, the role of SWI/SNF complexes in immune response and inflammatory diseases continues to attract significant attention. This review presents a summary of the significant functions of SWI/SNF complexes during the overall process from the development to the activation of innate and adaptive immune cells. In addition, the correlation between various SWI/SNF subunits and diverse inflammatory diseases is explored. Further investigations are warranted in terms of the mechanism of SWI/SNF complexes' preference for binding sites and opposite pro-/anti-inflammatory effects. In conclusion, further efforts are needed to evaluate the druggability of targeting SWI/SNF complexes in inflammatory diseases, and we hope this review will inspire the development of novel immune modulators in clinical practice.

Asthma is a chronic airway inflammatory disease that affects millions globally. Although glucocorticoids are a mainstay of asthma treatment, a subset of patients show resistance to these therapies, resulting in poor disease control and increased morbidity. The complex mechanisms underlying steroid-resistant asthma (SRA) involve Th1 and Th17 lymphocyte activity, neutrophil recruitment, and NLRP3 inflammasome activation. Recent studies provided evidence that innate lymphoid cells type 3 (ILC3s) might be potential therapeutic targets for non-eosinophilic asthma (NEA) and SRA. Like Th17 cells, ILC3s play crucial roles in immune responses, inflammation, and tissue homeostasis, contributing to disease severity and corticosteroid resistance in NEA. Biologics targeting ILC3-related pathways have shown promise in managing Th2-low asthma, suggesting new avenues for SRA treatment. This review aims to explore the risk factors for SRA, discuss the challenges and mechanisms underlying SRA, consolidate current findings on innate lymphoid cells, and elucidate their role in respiratory conditions. We present the latest findings on the involvement of ILC3s in human diseases and explore their potential mechanisms in SRA development. Furthermore, we review emerging therapeutic biologics targeting ILC3-related pathways in managing NEA and SRA. This review highlights current challenges, and emerging therapeutic strategies, and addresses a significant gap in asthma research, with implications for improving the management of steroid-resistant asthma.