{"title":"Neutrophils: a Central Point of Interaction Between Immune Cells and Nonimmune Cells in Rheumatoid Arthritis.","authors":"Zhaoran Wang, Yi Jiao, Wenya Diao, Tong Shi, Qishun Geng, Chaoying Wen, Jiahe Xu, Tiantian Deng, Xiaoya Li, Lu Zhao, Jienan Gu, Tingting Deng, Cheng Xiao","doi":"10.1007/s12016-025-09044-3","DOIUrl":"https://doi.org/10.1007/s12016-025-09044-3","url":null,"abstract":"<p><p>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.</p>","PeriodicalId":10423,"journal":{"name":"Clinical Reviews in Allergy & Immunology","volume":"68 1","pages":"34"},"PeriodicalIF":8.4,"publicationDate":"2025-03-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143728923","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Emerging Contaminants: An Important But Ignored Risk Factor for Psoriasis.","authors":"Leyi Huang, Yinli Zhou, Hui Xiao, Yajia Li, Zhiru Zhou, Ziyi Xiao, Yixuan Tong, Kun Hu, Yehong Kuang, Minxue Shen, Yi Xiao, Xiang Chen","doi":"10.1007/s12016-025-09043-4","DOIUrl":"https://doi.org/10.1007/s12016-025-09043-4","url":null,"abstract":"<p><p>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.</p>","PeriodicalId":10423,"journal":{"name":"Clinical Reviews in Allergy & Immunology","volume":"68 1","pages":"33"},"PeriodicalIF":8.4,"publicationDate":"2025-03-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143691210","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"The Impact of Menopause on Autoimmune and Rheumatic Diseases.","authors":"Francesca Motta, Nicoletta Di Simone, Carlo Selmi","doi":"10.1007/s12016-025-09031-8","DOIUrl":"10.1007/s12016-025-09031-8","url":null,"abstract":"<p><p>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.</p>","PeriodicalId":10423,"journal":{"name":"Clinical Reviews in Allergy & Immunology","volume":"68 1","pages":"32"},"PeriodicalIF":8.4,"publicationDate":"2025-03-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11928423/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143673318","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Immune Memory: A New Frontier in Treating Recurrent Inflammatory Skin Diseases.","authors":"Hang Yin, Jianru Chen, Chunying Li","doi":"10.1007/s12016-025-09039-0","DOIUrl":"https://doi.org/10.1007/s12016-025-09039-0","url":null,"abstract":"<p><p>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.</p>","PeriodicalId":10423,"journal":{"name":"Clinical Reviews in Allergy & Immunology","volume":"68 1","pages":"31"},"PeriodicalIF":8.4,"publicationDate":"2025-03-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143656238","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Implication of Immunobiological Function of Melanocytes in Dermatology.","authors":"Hejuan Zhang, Maomei Xia, Hongyang Li, Xuesi Zeng, Hong Jia, Wei Zhang, Jia Zhou","doi":"10.1007/s12016-025-09040-7","DOIUrl":"https://doi.org/10.1007/s12016-025-09040-7","url":null,"abstract":"<p><p>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.</p>","PeriodicalId":10423,"journal":{"name":"Clinical Reviews in Allergy & Immunology","volume":"68 1","pages":"30"},"PeriodicalIF":8.4,"publicationDate":"2025-03-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143647531","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"The Role of M<sup>6</sup>A Modification in Autoimmunity: Emerging Mechanisms and Therapeutic Implications.","authors":"Liyun Xu, Tian Shen, Yongzhen Li, Xiaochuan Wu","doi":"10.1007/s12016-025-09041-6","DOIUrl":"https://doi.org/10.1007/s12016-025-09041-6","url":null,"abstract":"<p><p>N6-methyladenosine (m<sup>6</sup>A), 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, m<sup>6</sup>A is crucial in forming innate defenses and adaptive immunity. This article provides a comprehensive overview of m<sup>6</sup>A 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 m<sup>6</sup>A-related enzymes (\"writers,\" \"erasers,\" and \"readers\") and summarizes recent advances in intervention strategies. By focusing on the mechanistic and therapeutic implications of m<sup>6</sup>A 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.</p>","PeriodicalId":10423,"journal":{"name":"Clinical Reviews in Allergy & Immunology","volume":"68 1","pages":"29"},"PeriodicalIF":8.4,"publicationDate":"2025-03-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143630179","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Xinxin Wu, Changya Liu, Caiyun Zhang, Le Kuai, Sheng Hu, Ning Jia, Jiankun Song, Wencheng Jiang, Qilong Chen, Bin Li
{"title":"The Role of Lactate and Lactylation in the Dysregulation of Immune Responses in Psoriasis.","authors":"Xinxin Wu, Changya Liu, Caiyun Zhang, Le Kuai, Sheng Hu, Ning Jia, Jiankun Song, Wencheng Jiang, Qilong Chen, Bin Li","doi":"10.1007/s12016-025-09037-2","DOIUrl":"https://doi.org/10.1007/s12016-025-09037-2","url":null,"abstract":"<p><p>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.</p>","PeriodicalId":10423,"journal":{"name":"Clinical Reviews in Allergy & Immunology","volume":"68 1","pages":"28"},"PeriodicalIF":8.4,"publicationDate":"2025-03-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143623503","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Th17 Response in Uveitis: A Double-Edged Sword in Ocular Inflammation and Immune Regulation.","authors":"Yuan Zong, Xue Tong, Wai Po Chong","doi":"10.1007/s12016-025-09038-1","DOIUrl":"10.1007/s12016-025-09038-1","url":null,"abstract":"<p><p>Uveitis involves a complex interplay of immune cell infiltration and cytokine imbalances, with Th17 cells playing a central role in this process. Th17 cells contribute to disease pathogenesis by promoting inflammation, recruiting additional immune cells, and directly damaging retinal tissues. This review discusses the current knowledge on therapeutic strategies targeting Th17-related cytokines, including cytokine blockade, small molecule inhibitors, and immunomodulatory approaches. Traditionally, Th17-related cytokines have been viewed as pro-inflammatory agents in uveitis. However, emerging research has highlighted the capacity of the Th17 response to express immunoregulatory cytokines, notably IL-10, IL-24, and TGF-β. This suggest that the Th17 response may have a dualistic role that includes immune suppression. In this review, we will discuss this paradoxical nature of Th17 cells in immune regulation and inflammation that they can both promote and mitigate uveitis. We expected that a deeper understanding of these mechanisms is imperative for the innovation of novel therapeutics that could consider the dual role of Th17 response in the pathogenesis of uveitis. By finely tuning the Th17 response to preserve retinal integrity and function, these new treatments could bring significant benefits to patients with uveitis. This review aims to shed light on the complexities of the Th17 response in uveitis and its implications for future therapeutic strategies.</p>","PeriodicalId":10423,"journal":{"name":"Clinical Reviews in Allergy & Immunology","volume":"68 1","pages":"26"},"PeriodicalIF":8.4,"publicationDate":"2025-03-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11903535/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143613584","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"The Role of IL-17 in Systemic Autoinflammatory Diseases: Mechanisms and Therapeutic Perspectives.","authors":"Jingyuan Zhang, Min Shen","doi":"10.1007/s12016-025-09042-5","DOIUrl":"https://doi.org/10.1007/s12016-025-09042-5","url":null,"abstract":"<p><p>Interleukin (IL)-17, a pro-inflammatory cytokine, plays a pivotal role in immune regulation by bridging innate and adaptive responses. Beyond its canonical involvement in T helper-17 cells-mediated immunity, IL-17 contributes significantly to the pathogenesis of systemic autoinflammatory diseases (SAIDs) including Familial Mediterranean Fever (FMF), nucleotide-binding oligomerization domain-like receptor protein 3 (NLRP3)-associated autoinflammatory diseases, and synovitis, acne, pustulosis, hyperostosis, and osteitis (SAPHO) syndrome. Dysregulated IL-17 signaling drives inflammasome activation, neutrophil recruitment, and chronic tissue inflammation. IL-17 inhibitors have demonstrated efficacy in refractory SAIDs, though challenges such as increased infection risks, paradoxical inflammatory reactions, and uncertainties regarding long-term safety persist. Currently, there is insufficient data to support the use of IL-17 inhibitors as first-line treatments, and their role in managing SAIDs is yet to be fully defined. This review highlights the mechanistic role of IL-17 in SAIDs and emerging therapeutic strategies, including IL-17-targeted monotherapies and combination approaches with IL-1 or tumor necrosis factor (TNF) inhibitors. Future research should focus on biomarker development, combination therapies, and long-term studies to optimize the safety and efficacy of IL-17-targeted therapies in SAIDs.</p>","PeriodicalId":10423,"journal":{"name":"Clinical Reviews in Allergy & Immunology","volume":"68 1","pages":"27"},"PeriodicalIF":8.4,"publicationDate":"2025-03-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143613506","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Hai-Yan Qin, Xian-Jun Xiao, Pei-Wen Xue, Di Qin, Si-Qi Wang, Ying Li, Yun-Zhou Shi, Li-Tao Pan
{"title":"The Role of Coagulation/Fibrinolysis Biomarkers in Pathophysiology, Disease Severity, and Treatment Response in Patients with Urticaria: A Scoping Review.","authors":"Hai-Yan Qin, Xian-Jun Xiao, Pei-Wen Xue, Di Qin, Si-Qi Wang, Ying Li, Yun-Zhou Shi, Li-Tao Pan","doi":"10.1007/s12016-025-09036-3","DOIUrl":"10.1007/s12016-025-09036-3","url":null,"abstract":"<p><p>The pathology of urticaria is complex. Recently, researchers have widely focused on the role that the coagulation/fibrinolysis system plays in the pathology of urticaria. The potential of coagulation/fibrinolysis biomarkers as disease severity or treatment response biomarkers remains uncertain, lacking comprehensive analysis in previous studies. Hence, we performed a scoping review to thoroughly analyze coagulation/fibrinolysis biomarkers that may predict disease progression and treatment response of urticaria. Data from 71 studies showed that chronic spontaneous urticaria (CSU) was the most-studied subtype (39 articles), with D-dimers being the most researched marker (56 articles). Twenty-one biomarkers were investigated, and ten biomarkers were significantly correlated with disease severity. Specifically, D-dimers (26 articles) and prothrombin fragment 1 + 2 (F<sub>1+2</sub>) (12 articles) plasma levels increased with exacerbation and decreased with remission. Biomarkers such as D-dimer also correlated significantly with inflammatory cytokines and complement, suggesting interactions among coagulation, immunity, and inflammation in the pathology of urticaria. While these biomarkers may predict treatment response, more evidence is needed. Additionally, anticoagulants such as warfarin, heparin sodium and tranexamic acid have been proved effective for urticaria. This review emphasizes that some coagulation/fibrinolysis biomarkers (such as D-dimer and F<sub>1+2</sub>) may be not only indicators of disease status but also potential predictors of treatment response. It aims to assist researchers and practitioners in gaining a better understanding of the close relationships among coagulation/fibrinolysis biomarkers, the condition of urticaria (especially chronic urticaria, CU), and its prognosis. It also provides new directions for future research on exploring treatment methods via the coagulation/fibrinolysis pathways.</p>","PeriodicalId":10423,"journal":{"name":"Clinical Reviews in Allergy & Immunology","volume":"68 1","pages":"25"},"PeriodicalIF":8.4,"publicationDate":"2025-03-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11893642/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143596358","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}