Clinical Reviews in Allergy & Immunology最新文献

The prevalence of food allergy continues to rise, posing a significant burden on health and quality of life. Research on antigenic epitope identification and hypoallergenic agent design is advancing allergen-specific immunotherapy (AIT). This review focuses on food allergens from the perspective of molecular allergology, provides an overview of integration of bioinformatics and experimental validation for epitope identification, highlights hypoallergenic agents designed based on epitope information, and offers a valuable guidance to the application of hypoallergenic agents in AIT. With the development of molecular allergology, the characterization of the amino acid sequence and structure of the allergen at the molecular level facilitates T-/B-cell epitope identification. Alignment of the identified epitopes in food allergens revealed that the amino acid sequence of T-/B-cell epitopes barely overlapped, providing crucial data to design allergen molecules as a promising form for treating (FA) food allergy. Manipulating antigenic epitopes can reduce the allergenicity of allergens to obtain hypoallergenic agents, thereby minimizing the severe side effects associated with AIT. Currently, hypoallergenic agents are mainly developed through synthetic epitope peptides, genetic engineering, or food processing methods based on the identified epitope. New strategies such as DNA vaccines, signaling molecules coupling, and nanoparticles are emerging to improve efficiency. Although significant progress has been made in designing hypoallergenic agents for AIT, the challenge in clinical translation is to determine the appropriate dose and duration of treatment to induce long-term immune tolerance.

Lymph nodes (LNs) are ovoid-shape capsulated structures interposed along the lymphatic vessels. Owing to their unique architecture, LNs place immune cell types in distinct compartments allowing effective contact of antigens to them. Their efficient function results in the concentration of antigens and bridging of antigen-presenting cells like DCs and B cells and cells of adaptive immunity (circulating B and T lymphocytes remaining in LNs to monitor antigens) to coordinate efficient immune responses. In a healthy LN, B cells are primarily clustered in lymphoid follicles, whereas T cells are organized in the deeper paracortex region. Mast cells (MCs) are among the immune cells; their normal presence or pathologic infiltration has been reported in LNs. MCs enter LNs through afferent lymphatic vessels and can be found in all compartments, ranging from subcapsular sinus to the deepest sections of medullary sinus; however, they are commonly found in the T cell zone and medullary sinus but rarely in follicles. In pathologies with LN involvement and solid tumors, features like MC accumulation and the anatomical region of accumulation within LNs differ based on the type of tumor and the organ. Moreover, MC accumulation in LNs may influence the trafficking of other cell types and immune responses. MCs out of LNs can facilitate the migration of DCs into LN, which is crucial for orchestrating immune responses, especially in vaccination; moreover, MCs play a role in the induction of peripheral tolerance. MC-released mediators including TNF from tissue-resident MCs and tryptase from LN-MCs mediate hyperplasia and extension of LN vasculature, respectively. MCs support lymphangiogenesis by releasing VEGF-C and VEGF-D in vivo. Further research on the role of MCs in LNs is anticipated due to the development of pharmaceuticals that impact MC survival or inhibit their activation. In this review, we summarize the current literature regarding the outcomes of MC presence in LNs with a focus on the MC-mediated immune responses in two categories: direct cell-to-cell and mediator-based interactions.

Congenital heart defects (CHD) are the most common major birth defects and one of the leading causes of death from congenital defects after birth. CHD can arise in pregnancy from the combination of genetic and non-genetic factors. The maternal immune activation (MIA) hypothesis is widely implicated in embryonic neurodevelopmental abnormalities. MIA has been found to be associated with the development of asthma, diabetes mellitus, and other diseases in the offspring. Given the important role of cardiac immune cells and cytokines in embryonic heart development, it is hypothesized that MIA may play a significant role in embryonic heart development. This review aims to stimulate further investigation into the relationship between MIA and CHD and to highlight the gaps in the knowledge. It evaluates the impact of MIA on CHD in the context of pregnancy complications, immune-related diseases, infections, and environmental and lifestyle factors. The review outlines the mechanisms by which immune cells and their secretome indirectly regulate the immuno-microenvironment of the embryonic heart by influencing placental development. Furthermore, the inflammatory cytokines cross the placenta to induce related reactions including oxidative stress in the embryonic heart directly. This review delineates the role of MIA in CHD and underscores the impact of maternal factors, especially immune factors, as well as the embryonic cardiac immuno-microenvironment, on embryonic heart development. This review extends our understanding of the importance of MIA in the pathogenesis of CHD and provides important insights into prenatal prevention and treatment strategies for this congenital condition.

Rheumatoid arthritis (RA) is a systemic autoimmune disease involving activation of the immune system and the infiltration of immune cells. As the first immune cells to reach the site of inflammation, neutrophils perform their biological functions by releasing many active substances and forming neutrophil extracellular traps (NETs). The overactivated neutrophils in patients with RA not only directly damage tissues but also, more importantly, interact with various other immune cells and broadly activate innate and adaptive immunity, leading to irreversible joint damage. However, owing to the pivotal role and complex influence of neutrophils in maintaining homoeostasis, the treatment of RA by targeting neutrophils is very difficult. Therefore, a comprehensive understanding of the interaction pathways between neutrophils and various other immune cells is crucial for the development of neutrophils as a new therapeutic target for RA. In this study, the important role of neutrophils in the pathogenesis of RA through their crosstalk with various other immune cells and nonimmune cells is highlighted. The potential of epigenetic modification of neutrophils for exploring the pathogenesis of RA and developing therapeutic approaches is also discussed. In addition, several models for studying cell‒cell interactions are summarized to support further studies of neutrophils in the context of RA.

Industrialization and modernization have changed the environment. A group of emerging contaminants (ECs) has been defined recently. Psoriasis, whose incidence has increased in recent years, is a relapsing immune-mediated disease carrying a heavy disease burden. The erythematous scaly plaque is a typical symptom and occurs on several parts of the body. In addition, psoriasis has many comorbidities, such as psoriatic arthritis, diabetes, and depression, damaging the quality of life of patients. IL-17, IL-12, IL-23, and TNF-alpha are important related cytokines. ECs can influence psoriasis through the immune system and inflammatory responses. Specific mechanisms include increasing pro-inflammatory cytokines such as TNF-α and IL-17, and activating immune cells such as macrophages. And for psoriasis patients, it is suggested to reduce the exposure of most ECs. However, the complex mechanisms involved have not been discussed together and concluded. In this review, we summarize the relationship between ECs and psoriasis, focusing on the immune system, especially the immune cells and cytokines. These results can help guide clinical treatment and long-term management of psoriasis.

The prevalence of autoimmune and rheumatological diseases is significantly higher in women, likely due to the effect of sex hormones influencing the development and function of the immune system, a phenomenon observed particularly during pregnancy. Oestrogens, in particular, appear to be a major factor in modulating the immune response, as their receptors are present in nearly all immune cells, where they regulate the expression of genes involved in inflammation. However, there is limited data on how menopause impacts autoimmune diseases, despite evidence suggesting that the menopausal perturbation of hormone levels may lead to the development of autoimmune conditions or alter the course of an already established disease. This review focuses on rheumatic conditions, aiming to provide a comprehensive understanding of how menopause influences the onset, progression, and clinical features of autoimmune diseases. The best evidence is available for rheumatoid arthritis and systemic lupus erythematosus, two paradigmatic autoimmune diseases in which menopause elicits opposite outcomes. Despite these data, there is a notable lack of evidence and research on the impact of menopause in other inflammatory arthritis and connective tissue diseases. This gap highlights a crucial area for future research and unmet needs to be addressed. Understanding how menopausal changes impact autoimmunity and rheumatic diseases will be crucial for improving the management of autoimmune and rheumatological diseases in women.

The recurrence of inflammatory skin diseases represents a significant challenge in clinical practice, primarily mediated by immune memory. In inflammatory skin diseases, immune memory encompasses adaptive immune memory, trained immunity, and inflammatory memory, which are conducted by adaptive immune cells, innate immune cells, and structural cells, respectively. Adaptive immune memory is established through gene rearrangement, leading to antigen-specific immune memory. In contrast, trained immunity and inflammatory memory are formed through epigenetic and metabolic reprogramming, resulting in non-specific immune memory. Different types of immune memory work synergistically to aggravate localized inflammation in recurrent inflammatory skin diseases. However, immune memory in specific cells, such as macrophages, may also play an immunoregulatory role under certain conditions. We reviewed the immune memory mechanisms in different inflammatory skin diseases and discussed future strategies for targeted regulation of the molecular mechanisms underlying immune memory, such as targeted biological agents and epigenetic modifications. Additionally, we explored the potential for precise regulation of immune memory and its application in personalized treatment for recurrent inflammatory skin diseases.

Melanocytes are essential for regulating pigmentation and providing photoprotection in human skin. Originating from neural crest cells, these cells migrate to the basal layer of the epidermis and hair follicles during embryogenesis. Melanosomes, the specialized, membrane-bound organelles are essential for melanin synthesis. Beyond their role in pigmentation, melanocytes exhibit complex immune functions, expressing a variety of immune-related markers and receptors, such as pattern recognition receptors (PRRs), major histocompatibility complex class II (MHC-II) molecules, CD40, intercellular adhesion molecule 1 (ICAM-1), and programmed death-ligand 1 (PD-L1). These receptors allow melanocytes to detect environmental signals and engage in the innate immune response. Furthermore, melanocytes release various immunomodulatory substances, including proinflammatory cytokines, chemokines, and damage-associated molecular patterns (DAMPs), contributing to immune regulation. The immune functions of melanocytes are significantly influenced by external factors such as ultraviolet radiation (UVR), the microbiome, and oxidative stress. In different skin diseases, these immune functions may vary. For example, vitiligo, a common hypopigmentary disorder, is primarily driven by an autoimmune response targeting melanocytes, giving rise to depigmentation and the appearance of white patches. In contrast, melanoma, a form of skin cancer that arises from melanocytes, is closely linked to UV exposure. This review highlights the diverse immunobiological functions of melanocytes and their implications in dermatology.

N6-methyladenosine (m⁶A), a prevalent and essential RNA modification, serves a key function in driving autoimmune disease pathogenesis. By modulating immune cell development, activation, migration, and polarization, as well as inflammatory pathways, m⁶A is crucial in forming innate defenses and adaptive immunity. This article provides a comprehensive overview of m⁶A modification features and reveals how its dysregulation affects the intensity and persistence of immune responses, disrupts immune tolerance, exacerbates tissue damage, and promotes the development of autoimmunity. Specific examples include its contributions to systemic autoimmune disorders like lupus and rheumatoid arthritis, as well as conditions that targeting specific organs like multiple sclerosis and type 1 diabetes. Furthermore, this review explores the therapeutic promise of target m⁶A-related enzymes ("writers," "erasers," and "readers") and summarizes recent advances in intervention strategies. By focusing on the mechanistic and therapeutic implications of m⁶A modification, this review sheds light on its role as a promising tool for both diagnosis and treatment in autoimmune disorders, laying the foundation for advancements in customized medicine.

Historically, lactate has been considered merely a metabolic byproduct. However, recent studies have revealed that lactate plays a much more dynamic role, acting as an immune signaling molecule that influences cellular communication, through the process of "lactate shuttling." Lactylation, a novel post-translational modification, is directly derived from lactate and represents an emerging mechanism through which lactate exerts its effects on cellular function. It has been shown to directly affect immune cells by modulating the activation of pro-inflammatory and anti-inflammatory pathways. This modification influences the expression of key immune-related genes, thereby impacting immune cell differentiation, cytokine production, and overall immune response. In this review, we focused on the role of lactate and lactylation in the dysregulation of immune responses in psoriasis and its relapse. Additionally, we discuss the potential applications of targeting lactate metabolism and lactylation modifications in the treatment of psoriasis, alongside the investigation of artificial intelligence applications in advancing lactate and lactylation-focused drug development, identifying therapeutic targets, and enabling personalized medical decision-making. The significance of this review lies in its comprehensive exploration of how lactate and lactylation contribute to immune dysregulation, offering a novel perspective for understanding the metabolic and epigenetic changes associated with psoriasis. By identifying the roles of these pathways in modulating immune responses, this review provides a foundation for the development of new therapeutic strategies that target these mechanisms.