Clinical Reviews in Allergy & Immunology最新文献

Allergic conjunctivitis (AC) is a common ophthalmic disease, ranging from mild, self-limiting forms to severe, vision-threatening conditions such as vernal keratoconjunctivitis and atopic keratoconjunctivitis. Its pathogenesis originates from the interplay between genetic predisposition and complex environmental factors, manifesting as a complex pathophysiological network. This review comprehensively elucidates recent advancements in the etiology and pathogenesis of AC. Key etiological drivers include Ig(Ig: Immunoglobulin) E-mediated reactions due to allergen sensitization, genetic susceptibility, and escalating environmental impacts, such as climate change, air pollution, and modern lifestyles influencing immune development and allergen exposure. Its pathogenesis is characterized by complex immune cell activation and crosstalk; dysregulation of lipid mediators; an intricate cytokine network predominantly driven by Th2(Th2: T helper 2) cytokines and alarmins that often signal via the JAK‒STAT(JAK‒STAT: Janus Kinase- Signal Transducer and Activator of Transcription) pathway; and a significant neuroimmune imbalance leading to neurogenic inflammation and persistent itch. Furthermore, epithelial barrier dysfunction, ocular surface microbiome dysbiosis, and epigenetic modifications are increasingly recognized as crucial regulatory factors. This review also highlights the ongoing challenges in addressing AC heterogeneity, pursuing personalized medicine, improving diagnostic methods, and developing effective preventive strategies, including allergen immunotherapy. Ultimately, integrating multidimensional data from cutting-edge research holds the promise of achieving more precise and personalized AC management, thereby improving outcomes for AC patients worldwide.

In the intricate regulation of gene expression, multiple regulatory elements play crucial roles. Among these, enhancers stand out as important elements that can boost the activity of promoters and make target genes more likely to be transcribed. Recent studies have revealed that sequence variations and gene rearrangements in enhancer regions could disrupt enhancer-promoter interactions, contributing to disease susceptibility and developmental abnormalities. Enhancer dysregulation is associated with numerous pathological conditions, spanning malignancies, autoimmune diseases, cardiovascular pathologies, and neurodegenerative ailments. Although the advent of high-throughput sequencing has enabled comprehensive enhancer profiling across the genome, elucidating their precise functional mechanisms continues to pose significant challenges. This review summarizes the structural features, identification methodologies, transcriptional regulatory mechanisms, and pathogenic contributions of enhancers in autoimmune diseases. Furthermore, we highlight emerging enhancer-based therapeutic strategies, offering novel insights for the targeted treatment of immune-related disorders. Additionally, we explore the role of phase separation in enhancer regulation and its potential association with autoimmune pathogenesis, proposing phase separation modulation as a promising therapeutic avenue.

Islet macrophages are considered to be irreplaceable in maintaining the immune microenvironment homeostasis. The M1/M2 imbalance can trigger the initiation of islet autoimmunity and persists throughout the entire process of type 1 diabetes. The identification of macrophage transcriptional clusters and phenotypes by single-cell sequencing has facilitated in-depth studies on the role of macrophages in the pathogenesis of type 1 diabetes. Macrophages exert extensive endocrine and paracrine effects on the islets by secreting various bioactive chemicals, especially exosomes, which facilitate cell-cell communication. Resident islet macrophages directly influence the biological properties of islet tissue. Meanwhile, the interaction between macrophages and islet cells is bidirectional. Cell-cell interactions also closely govern the polarization and activity of macrophages. An imbalance in the transition from M2 to M1 macrophages may lead to inflammation and islet dysfunction. Here, we have discussed the latest research progress on macrophages in the islet immune microenvironment homeostasis, the mechanisms of interactions between macrophages and islet cells in type 1 diabetes, and analyzed the possible clinical consequences. Furthermore, we highlighted emerging technologies for non-invasive detection of macrophages and summarized how therapeutic targeting of macrophages may be beneficial for patients with type 1 diabetes.

Idiopathic inflammatory myopathies (IIMs) are a group of rare autoimmune diseases in which several subtypes, primarily dermatomyositis (DM), are associated with a high risk of malignancy. Although the relationship between the pathogenesis of IIMs and co-occurring malignancy is poorly understood, there is a growing evidence base for specific risk factors which are associated with cancer-associated myositis (CAM), including myositis-specific or myositis-associated autoantibodies (MSAs/MAAs). In addition, given that patients with different subtypes of IIMs, as classified according to clinical manifestations or serum autoantibody measurement, exhibit heterogeneity in tumorigenesis, further research is urgently needed to explore the pathogenesis of CAM, in order to develop novel biomarkers and therapeutic alternatives for patients. This review discusses the risk and protective factors for CAM using the available evidence, thereby offering fresh insights into its pathogenesis, screening, and management strategies and highlighting possible future breakthroughs and obstacles in this field.

Background: The characteristics of Behçet's disease (BD) in individuals of Sub-Saharan ancestry (sub-SA) are poorly understood.

Methods: Herein, we conducted a PRISMA-compliant systematic review using the PubMed/Medline, Scopus, and Web of Science databases. Articles published up to September 1, 2023 were searched with the following keywords: "Behçet's disease" OR "Behcet's syndrome" AND "sub-Saharan African" OR "Black" OR "African". Data on the year, type and country of study, sample size, region of origin, nationality, age, sex, time to diagnosis, death, HLAB51 status, mucosal, and organ involvement were collected. Involvement of the central nervous system was retained on the basis of objective criteria, and dichotomized into parenchymal or non-parenchymal/vascular lesions. The pooled frequency of patients' main characteristics was calculated using a DerSimonian-Laird random-effects meta-analysis.

Results: This study included 42 full-text reports, with study periods ranging from 1970 to 2023. Overall, 230 adult patients (69% of males) were included, of whom 195 (85%) were from sub-Saharan African countries, 22 (10%) patients were from the Caribbean, and 13 (5%) patients were from the Americas, including 12 African Americans, and 1 African Brazilian. Oral and genital ulcers were reported in 98% [95% CI 91 to 100%] and 85% [72 to 92%], respectively. Ocular involvement occurred in 43% [31 to 56%] of patients. Central nervous system (CNS) involvement affected 39% [25 to 54] of the patients. Among them, 30% of patients had a cerebro-vascular disease, and 72% had a parenchymal involvement. The patients were mostly treated with oral steroids and colchicine, and remission was achieved in 35/54 (65%) patients, but 15 (69%) of them suffered severe sequelae, particularly ophthalmological and neurological.

Conclusion: Behçet's disease in patients of sub-Saharan ancestry appears to be predominantly HLA B51/B5-negative, and more severe than in other ethnicities, owing to a high prevalence of CNS involvement.

Inflammatory skin diseases and skin cancers are usually accompanied by metabolic comorbidities or altered metabolic status. Metabolomic analysis indicates that patients with inflammatory skin diseases and skin cancers exhibit altered metabolites, including glycans, lipids, and amino acids. This suggests that metabolic reprogramming may play a pivotal role in the pathogenesis of these skin diseases. The solute carrier (SLC) superfamily is responsible for the transport of a range of metabolites, which may serve as crucial intermediate links in the metabolic reprogramming of diseases. Nevertheless, research on the SLC superfamily in skin diseases remains limited, and the development of its drug targets is even more scarce. Therefore, this review is devoted to elucidating our current understanding of the role of the SLC family in the pathogenesis of inflammatory skin diseases and skin cancers, with a particular emphasis on its role in metabolic reprogramming. In doing so, we aim to provide a reference point for the subsequent development of drug targets for the SLC family in skin diseases.

Psoriasis is a chronic, immune-mediated inflammatory disorder marked by a complex interplay between genetic predisposition, cytokine dysregulation, and environmental triggers. Originally perceived as a superficial dermatological condition, it is now recognized as a systemic disease with far-reaching health implications. Advances in molecular genetics have uncovered over 80 susceptibility loci, with key variants such as HLA-C*06:02, IL23R, and CARD14 contributing to the multifactorial nature of the disorder. Central to its pathogenesis is the aberrant activation of the IL-23/Th17 axis, resulting in excessive production of proinflammatory cytokines that promote rapid keratinocyte proliferation and sustained inflammation. Epigenetic modifications further influence gene expression, while interactions with environmental factors, such as mechanical stress, ultraviolet exposure, and air pollution, exacerbate the inflammatory cascade. Recent progress in targeted therapeutic strategies, notably biologic agents and small molecule inhibitors, has transformed the treatment landscape by specifically modulating these pathogenic pathways. Such innovations are paving the way toward personalized medicine, aiming to optimize therapeutic outcomes and reduce the overall disease burden. This review offers a comprehensive synthesis of current knowledge on the genetic, immunologic, and molecular mechanisms underlying psoriasis. The review emphasizes recent advances in targeted therapies underlining the potential for translational applications that address both cutaneous manifestations and systemic inflammation. It also explores global disparities in psoriasis care and the need for inclusive approaches that bridge disparities and promote equitable, innovative disease management strategies.

Alterations in gut microbiota composition are increasingly recognized as key contributors to autoimmune disease pathogenesis. While dominant phyla such as Firmicutes and Bacteroidetes have been extensively studied at the phylum level, the immunomodulatory roles of specific members within these groups particularly the abundant but mechanistically underexplored Faecalibacterium prausnitzii (a member of Firmicutes) and Akkermansia muciniphila (of Verrucomicrobia) remain insufficiently characterized. In particular, current literature primarily focuses on associative findings, and integrated analyses elucidating disease-specific mechanisms and therapeutic relevance are still lacking. In this review, we synthesize mechanistic and disease-specific evidence regarding these two bacterial species across six autoimmune diseases, including systemic lupus erythematosus (SLE), type 1 diabetes (T1D), and rheumatoid arthritis (RA). F. prausnitzii is consistently depleted in autoimmune contexts and exerts protective effects through multiple mechanisms, including short-chain fatty acid (SCFA) production, histone deacetylase (HDAC) inhibition, Treg induction, secretion of microbial anti-inflammatory molecules (MAM), enhancement of epithelial barrier integrity, and modulation of pro- and anti-inflammatory cytokine responses. In contrast, A. muciniphila modulates mucosal immunity via Toll-like receptor 2 (TLR2) activation and tight junction enhancement but exhibits more variable patterns depending on disease and host context. This review offers an integrative framework comparing how these two taxa influence shared immune pathways such as the Th17/Treg axis, SCFA-G protein-coupled receptor (GPR) signaling, and epithelial barrier modulation across distinct autoimmune phenotypes. We also discuss therapeutic implications, including their roles as next-generation probiotics and the translational challenges of clinical application. By focusing on two mechanistically distinct but clinically relevant microbes, this review bridges current knowledge gaps and highlights promising directions for precision microbiome interventions in autoimmune diseases.

Decades of research have elucidated diverse aspects of neuroimmunology. This interdisciplinary field originates from the observation almost one century ago that local sensory signals in the skin regulate mast cell degranulation, a key event in allergic reactions. With this historical perspective, the current research has expanded in different dimensions, including hormonal mechanisms, direct immunomodulation by neural signals, and immune barriers in the central nervous system. Notably, neural innervations in the gastrointestinal tract can establish complex crosstalk with various immune cells through the release of specific neurotransmitters (e.g., norepinephrine or acetylcholine) or neuropeptides (e.g., calcitonin gene-related peptide), which engage the corresponding receptors expressed on immune cells (e.g., mast cells or innate lymphoid cells). Such neuroimmune interactions have become a frontier topic in biomedical science over the past years. In this review, we aim to summarize the current knowledge of neuroimmunology, with a focus on the gastrointestinal tract. We then highlight the implications of such neuroimmune interactions in the disease context of food allergy.