Pub Date : 2025-07-06DOI: 10.1016/j.clim.2025.110559
Manqi Tang , Weicheng Shen , Yanying Liu
Immunoglobulin G4-Related Disease (IgG4-RD) is a recently characterized systemic autoimmune disorder marked by multiorgan inflammation and progressive fibrosis. It can affect nearly any organ and may lead to serious clinical consequences. Despite recent progress in developing animal models, therapeutic options for IgG4-RD remain limited, and the pathogenic mechanisms underlying immune dysregulation and fibrosis are still not fully understood. To support mechanistic and therapeutic research, both humanized and non-humanized animal models have been established in recent years. However, the unique biological features of the IgG4 molecule, together with genetic differences between humans and mice, present significant challenges to conventional mouse models. Although several models replicate certain features of IgG4-RD, none fully recapitulate the pathological hallmarks observed in patients. This review critically examines the strengths and limitations of current experimental models and outlines future directions for improving IgG4-RD model systems to better reflect human disease pathogenesis.
{"title":"Animal models of IgG4-related disease","authors":"Manqi Tang , Weicheng Shen , Yanying Liu","doi":"10.1016/j.clim.2025.110559","DOIUrl":"10.1016/j.clim.2025.110559","url":null,"abstract":"<div><div>Immunoglobulin G4-Related Disease (IgG4-RD) is a recently characterized systemic autoimmune disorder marked by multiorgan inflammation and progressive fibrosis. It can affect nearly any organ and may lead to serious clinical consequences. Despite recent progress in developing animal models, therapeutic options for IgG4-RD remain limited, and the pathogenic mechanisms underlying immune dysregulation and fibrosis are still not fully understood. To support mechanistic and therapeutic research, both humanized and non-humanized animal models have been established in recent years. However, the unique biological features of the IgG4 molecule, together with genetic differences between humans and mice, present significant challenges to conventional mouse models. Although several models replicate certain features of IgG4-RD, none fully recapitulate the pathological hallmarks observed in patients. This review critically examines the strengths and limitations of current experimental models and outlines future directions for improving IgG4-RD model systems to better reflect human disease pathogenesis.</div></div>","PeriodicalId":10392,"journal":{"name":"Clinical immunology","volume":"280 ","pages":"Article 110559"},"PeriodicalIF":4.5,"publicationDate":"2025-07-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144590537","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-06-28DOI: 10.1016/j.clim.2025.110548
Jayhyun Kim , Jung Gon Kim , Yingjin Li , Sungyong You , Naeun Lee , Wan-Uk Kim
Lymphocyte-specific protein-1 (LSP1) is known to negatively regulate T cell migration in autoimmune diseases. However, its role in the development of T cell-dependent Sjögren's syndrome remains unknown. In this study, we found that LSP1 expression was decreased in T cells in salivary glands (SGs) of mice with experimental Sjögren's syndrome, accompanied by enhanced infiltration of leukocytes into SGs. Moreover, Lsp1−/− mice had higher frequency of IL-17A-expressing T cells in cervical lymph nodes as well as increased severity in SGs than WT mice. Concurrently, LSP1 expression was reduced in human T cells of primary Sjögren's syndrome (pSS) patient. Particularly, pSS patients showed an increased Th17 cells, which inversely correlated with LSP1 expression. Taken together, these findings suggest that LSP1 deficiency promote Th17 cell development and exacerbation of pSS. LSP1 might be a potential therapeutic target to regulate Th17 response and to treat autoimmune diseases like pSS.
{"title":"LSP1 deficiency increases IL-17-expressing T cells and accelerates primary Sjögren's syndrome","authors":"Jayhyun Kim , Jung Gon Kim , Yingjin Li , Sungyong You , Naeun Lee , Wan-Uk Kim","doi":"10.1016/j.clim.2025.110548","DOIUrl":"10.1016/j.clim.2025.110548","url":null,"abstract":"<div><div>Lymphocyte-specific protein-1 (LSP1) is known to negatively regulate T cell migration in autoimmune diseases. However, its role in the development of T cell-dependent Sjögren's syndrome remains unknown. In this study, we found that LSP1 expression was decreased in T cells in salivary glands (SGs) of mice with experimental Sjögren's syndrome, accompanied by enhanced infiltration of leukocytes into SGs. Moreover, <em>Lsp1</em><sup><em>−/−</em></sup> mice had higher frequency of IL-17A-expressing T cells in cervical lymph nodes as well as increased severity in SGs than WT mice. Concurrently, LSP1 expression was reduced in human T cells of primary Sjögren's syndrome (pSS) patient. Particularly, pSS patients showed an increased Th17 cells, which inversely correlated with LSP1 expression. Taken together, these findings suggest that LSP1 deficiency promote Th17 cell development and exacerbation of pSS. LSP1 might be a potential therapeutic target to regulate Th17 response and to treat autoimmune diseases like pSS.</div></div>","PeriodicalId":10392,"journal":{"name":"Clinical immunology","volume":"280 ","pages":"Article 110548"},"PeriodicalIF":4.5,"publicationDate":"2025-06-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144526684","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-06-24DOI: 10.1016/j.clim.2025.110550
Shaowei Pan , Xiaoyun Xie , Tong Li , Shiyao Wu , Ying Jiang , Huali Zhang , Xiaoli Zhang
Systemic lupus erythematosus (SLE) is often accompanied by hematological complications, with T follicular helper (Tfh) cells playing a pivotal role in its pathogenesis. This study explores the relationship between bone marrow Tfh and Interleukin-33 (IL-33) in SLE patients with hematological abnormalities. Using flow cytometry and ELISA, we found elevated percentages of bone marrow ST2+ Tfh cells in SLE patients, which correlated with disease activity, white blood cell count, and B cell percentage. Increased bone marrow IL-33 and BLyS levels were also observed. Keyhole-limpet hemocyanin (KLH)-immunized mouse model demonstrated IL-33-dependent Tfh expansion, while ST2 knockdown reduced Tfh frequency. In vitro co-culture experiments demonstrated that the IL-33/ST2 axis plays a pivotal role in enhancing the function of Tfh and T peripheral helper (Tph) cells, thereby promoting B cell differentiation into antibody-secreting plasma cells. These findings establish IL-33/ST2 as a key regulator of humoral immunity and a potential therapeutic target for SLE.
{"title":"IL-33 regulates abnormally increased expression of ST2 in bone marrow follicular helper T cell in SLE with hematological abnormalities","authors":"Shaowei Pan , Xiaoyun Xie , Tong Li , Shiyao Wu , Ying Jiang , Huali Zhang , Xiaoli Zhang","doi":"10.1016/j.clim.2025.110550","DOIUrl":"10.1016/j.clim.2025.110550","url":null,"abstract":"<div><div>Systemic lupus erythematosus (SLE) is often accompanied by hematological complications, with T follicular helper (Tfh) cells playing a pivotal role in its pathogenesis. This study explores the relationship between bone marrow Tfh and Interleukin-33 (IL-33) in SLE patients with hematological abnormalities. Using flow cytometry and ELISA, we found elevated percentages of bone marrow ST2+ Tfh cells in SLE patients, which correlated with disease activity, white blood cell count, and B cell percentage. Increased bone marrow IL-33 and BLyS levels were also observed. Keyhole-limpet hemocyanin (KLH)-immunized mouse model demonstrated IL-33-dependent Tfh expansion, while ST2 knockdown reduced Tfh frequency. In vitro co-culture experiments demonstrated that the IL-33/ST2 axis plays a pivotal role in enhancing the function of Tfh and T peripheral helper (Tph) cells, thereby promoting B cell differentiation into antibody-secreting plasma cells. These findings establish IL-33/ST2 as a key regulator of humoral immunity and a potential therapeutic target for SLE.</div></div>","PeriodicalId":10392,"journal":{"name":"Clinical immunology","volume":"279 ","pages":"Article 110550"},"PeriodicalIF":4.5,"publicationDate":"2025-06-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144505039","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-06-24DOI: 10.1016/j.clim.2025.110549
Nabil Belfeki , Nouha Ghriss , Alexandre Le Joncour , David Saadoun
Behçet's disease (BD) is a chronic, multisystemic inflammatory vasculitis affecting veins and arteries. Its etiopathogenesis remains unclear but is thought to result from genetic predisposition combined with environmental triggers. Recent genome-wide association studies (GWAS) have linked various genetic polymorphisms (e.g., HLA*B51, ERAP1) to an increased risk of BD, with particular focus on cytokine-related gene variants. Infectious agents, such as Streptococcus species and herpes simplex virus, along with oral and intestinal dysbiosis and molecular mimicry, are key environmental triggers of innate immune inflammation, which is further amplified by adaptive immune responses. The innate immune system's primary cells, including neutrophils and NK cells, are upregulated, leading to an overproduction of proinflammatory cytokines. Additionally, an imbalance in T cell populations, characterized by a decrease in Tregs and expansion of Th1 and Th17 cells, contributes to disease pathogenesis. This review provides an overview of recent advances in understanding BD's etiopathogenesis.
{"title":"Etiopathogenesis of Behçet's disease: A systematic literature review","authors":"Nabil Belfeki , Nouha Ghriss , Alexandre Le Joncour , David Saadoun","doi":"10.1016/j.clim.2025.110549","DOIUrl":"10.1016/j.clim.2025.110549","url":null,"abstract":"<div><div>Behçet's disease (BD) is a chronic, multisystemic inflammatory vasculitis affecting veins and arteries. Its etiopathogenesis remains unclear but is thought to result from genetic predisposition combined with environmental triggers. Recent genome-wide association studies (GWAS) have linked various genetic polymorphisms (e.g., HLA*B51, ERAP1) to an increased risk of BD, with particular focus on cytokine-related gene variants. Infectious agents, such as <em>Streptococcus</em> species and herpes simplex virus, along with oral and intestinal dysbiosis and molecular mimicry, are key environmental triggers of innate immune inflammation, which is further amplified by adaptive immune responses. The innate immune system's primary cells, including neutrophils and NK cells, are upregulated, leading to an overproduction of proinflammatory cytokines. Additionally, an imbalance in T cell populations, characterized by a decrease in Tregs and expansion of Th1 and Th17 cells, contributes to disease pathogenesis. This review provides an overview of recent advances in understanding BD's etiopathogenesis.</div></div>","PeriodicalId":10392,"journal":{"name":"Clinical immunology","volume":"279 ","pages":"Article 110549"},"PeriodicalIF":4.5,"publicationDate":"2025-06-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144505038","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-06-23DOI: 10.1016/j.clim.2025.110547
Haris Afridi, Kainat Afzal
{"title":"Comment on: “A national survey of four decades of hereditary angioedema prophylaxis” — The emerging role of Garadacimab","authors":"Haris Afridi, Kainat Afzal","doi":"10.1016/j.clim.2025.110547","DOIUrl":"10.1016/j.clim.2025.110547","url":null,"abstract":"","PeriodicalId":10392,"journal":{"name":"Clinical immunology","volume":"279 ","pages":"Article 110547"},"PeriodicalIF":4.5,"publicationDate":"2025-06-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144491694","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-06-19DOI: 10.1016/j.clim.2025.110546
Yi-Kai Liu , Meng Hao , Fan Yang , Ke-Xin Jing , Shun Zhao , Changhao Wu , Hai-Feng Pan
Scavenger receptors (SRs) belong to a large receptor family expressed on immune and non- immune cells. Initially, SRs are regarded as removers able to recognize and clear modified lipoproteins; However, it is now realized that they are pattern recognition receptors (PRRs) that identify damage-associated molecular pattern (DAMP) and pathogen-associated molecular patterns (PAMPs). The wide range of ligands that bind to SRs demonstrates their diverse functions, including pathogen clearance, lipid transport, cellular differentiation, and signaling pathway activation. Previous studies have revealed the significance of SRs in regulating innate immunity and adaptive immunity. Recently, a large body of evidence further indicates the involvement of SRs in autoimmune diseases, including systemic lupus erythematosus (SLE), rheumatoid arthritis (RA), multiple sclerosis (MS), type 1 diabetes (T1D) and inflammatory bowel disease (IBD). In this comprehensive review, we will summarize molecular structure and immunological functions of different types of SRs, and discuss the recent insights into the involvement of SRs in the development and pathogenesis of autoimmune diseases and their clinical implications and therapeutic potential.
{"title":"Scavenger receptors: An auspicious therapeutic target for autoimmune diseases","authors":"Yi-Kai Liu , Meng Hao , Fan Yang , Ke-Xin Jing , Shun Zhao , Changhao Wu , Hai-Feng Pan","doi":"10.1016/j.clim.2025.110546","DOIUrl":"10.1016/j.clim.2025.110546","url":null,"abstract":"<div><div>Scavenger receptors (SRs) belong to a large receptor family expressed on immune and non- immune cells. Initially, SRs are regarded as removers able to recognize and clear modified lipoproteins; However, it is now realized that they are pattern recognition receptors (PRRs) that identify damage-associated molecular pattern (DAMP) and pathogen-associated molecular patterns (PAMPs). The wide range of ligands that bind to SRs demonstrates their diverse functions, including pathogen clearance, lipid transport, cellular differentiation, and signaling pathway activation. Previous studies have revealed the significance of SRs in regulating innate immunity and adaptive immunity. Recently, a large body of evidence further indicates the involvement of SRs in autoimmune diseases, including systemic lupus erythematosus (SLE), rheumatoid arthritis (RA), multiple sclerosis (MS), type 1 diabetes (T1D) and inflammatory bowel disease (IBD). In this comprehensive review, we will summarize molecular structure and immunological functions of different types of SRs, and discuss the recent insights into the involvement of SRs in the development and pathogenesis of autoimmune diseases and their clinical implications and therapeutic potential.</div></div>","PeriodicalId":10392,"journal":{"name":"Clinical immunology","volume":"279 ","pages":"Article 110546"},"PeriodicalIF":4.5,"publicationDate":"2025-06-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144336007","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-06-18DOI: 10.1016/j.clim.2025.110545
Mattia Russel Pantalone , Xinling Xu , Nerea Martín Almazán , Christina Gerstner , Marie Fischer , Marika Kvarnström , Cecilia Söderberg-Nauclér , Marie Wahren-Herlenius , Afsar Rahbar
Sjögren's disease (SD) is a chronic autoimmune disease characterized by immune-mediated damage to salivary and lacrimal glands. This study aimed to explore the potential link between SD and human cytomegalovirus (HCMV), by analyzing presence of HCMV proteins in salivary gland tissue specimens and prevalence of HCMV-specific antibodies in serum samples from SD patients and controls. HCMV-immediate early (IE) and late proteins (LA and pp65) were highly abundant in tissue specimens from SD patients (88.9 %, 69.2 %, 45.8 %, respectively), and less abundant in patients with Sicca symptoms without SD (70.5 %, 20.0 %, 12.5 %, respectively). Samples in the SD group were also positive at higher scores for the HCMV proteins than Sicca symptom patients without SD. IgM prevalence was higher in SD patients than in healthy controls (32.1 % vs. 13.4 %, P = 0.04) and HCMV-IgG titers were higher (P < 0.0001). Understanding the potential role of HCMV in SD pathogenesis may contribute to advancements in disease prevention and treatment.
{"title":"High activity of human cytomegalovirus in patients with Sjögren's disease","authors":"Mattia Russel Pantalone , Xinling Xu , Nerea Martín Almazán , Christina Gerstner , Marie Fischer , Marika Kvarnström , Cecilia Söderberg-Nauclér , Marie Wahren-Herlenius , Afsar Rahbar","doi":"10.1016/j.clim.2025.110545","DOIUrl":"10.1016/j.clim.2025.110545","url":null,"abstract":"<div><div>Sjögren's disease (SD) is a chronic autoimmune disease characterized by immune-mediated damage to salivary and lacrimal glands. This study aimed to explore the potential link between SD and human cytomegalovirus (HCMV), by analyzing presence of HCMV proteins in salivary gland tissue specimens and prevalence of HCMV-specific antibodies in serum samples from SD patients and controls. HCMV-immediate early (IE) and late proteins (LA and pp65) were highly abundant in tissue specimens from SD patients (88.9 %, 69.2 %, 45.8 %, respectively), and less abundant in patients with Sicca symptoms without SD (70.5 %, 20.0 %, 12.5 %, respectively). Samples in the SD group were also positive at higher scores for the HCMV proteins than Sicca symptom patients without SD. IgM prevalence was higher in SD patients than in healthy controls (32.1 % vs. 13.4 %, <em>P</em> = 0.04) and HCMV-IgG titers were higher (<em>P</em> < 0.0001). Understanding the potential role of HCMV in SD pathogenesis may contribute to advancements in disease prevention and treatment.</div></div>","PeriodicalId":10392,"journal":{"name":"Clinical immunology","volume":"279 ","pages":"Article 110545"},"PeriodicalIF":4.5,"publicationDate":"2025-06-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144336379","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-06-15DOI: 10.1016/j.clim.2025.110540
Valentina Natoli , Amandine Charras , Megan S.R. Hasoon , Andrea L. Jorgensen , Eve M.D. Smith , Eva Caamaño Gutiérrez , Michael W. Beresford , Christian M. Hedrich
Juvenile-onset systemic lupus erythematosus (jSLE) is a complex autoimmune/inflammatory disease in which genetic factors likely contribute to pathophysiology and clinical expression. This study explored associations between general (alternate allele counts; AAC) and gene-specific (alternate allele scores; GAAS) sequence variability, age at onset, sex, ancestry, disease activity/severity, organ involvement and treatments in jSLE. 289 participants from the UK JSLE Cohort Study underwent panel sequencing of 62 genes/genomic regions. Weighted AAC and GAAS were calculated. Correlation analyses and generalized linear models assessed associations between genetic burden, ancestry, age at diagnosis and clinical variables. AAC inversely correlated with age at diagnosis (R = -0.15, p = 0.01), primarily driven by South Asians (R = -0.28, p < 0.001). African/Caribbean patients exhibited higher AAC (p < 0.001). Clinical variables, including severity of renal involvement (ACP5, ITGAM, LYN, p < 0.001; TNFAIP3, p = 0.007), associated with GAAS. Genetic variability likely contributes to early disease expression and severity in jSLE, supporting patient stratification and personalised care.
{"title":"Genetic variability associates with ancestry, age at disease onset, organ involvement and disease severity in juvenile-onset systemic lupus erythematosus","authors":"Valentina Natoli , Amandine Charras , Megan S.R. Hasoon , Andrea L. Jorgensen , Eve M.D. Smith , Eva Caamaño Gutiérrez , Michael W. Beresford , Christian M. Hedrich","doi":"10.1016/j.clim.2025.110540","DOIUrl":"10.1016/j.clim.2025.110540","url":null,"abstract":"<div><div>Juvenile-onset systemic lupus erythematosus (jSLE) is a complex autoimmune/inflammatory disease in which genetic factors likely contribute to pathophysiology and clinical expression. This study explored associations between general (alternate allele counts; AAC) and gene-specific (alternate allele scores; GAAS) sequence variability, age at onset, sex, ancestry, disease activity/severity, organ involvement and treatments in jSLE. 289 participants from the UK JSLE Cohort Study underwent panel sequencing of 62 genes/genomic regions. Weighted AAC and GAAS were calculated. Correlation analyses and generalized linear models assessed associations between genetic burden, ancestry, age at diagnosis and clinical variables. AAC inversely correlated with age at diagnosis (R = -0.15, <em>p</em> = 0.01), primarily driven by South Asians (R = -0.28, <em>p</em> < 0.001). African/Caribbean patients exhibited higher AAC (p < 0.001). Clinical variables, including severity of renal involvement (<em>ACP5</em>, <em>ITGAM</em>, <em>LYN</em>, p < 0.001; <em>TNFAIP3</em>, <em>p</em> = 0.007), associated with GAAS. Genetic variability likely contributes to early disease expression and severity in jSLE, supporting patient stratification and personalised care.</div></div>","PeriodicalId":10392,"journal":{"name":"Clinical immunology","volume":"279 ","pages":"Article 110540"},"PeriodicalIF":4.5,"publicationDate":"2025-06-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144316037","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-06-14DOI: 10.1016/j.clim.2025.110543
Baochun Luo , Sifan Liu , Lei Zheng , Baiwen Zhang , Yaxin Shang , Tong Shang , Jia Zheng , Binglin Kuang , Wei Zou
Intracerebral hemorrhage (ICH) is the most lethal subtype of stroke, making the effective prevention and treatment of inflammatory secondary injury crucial. Recently, the role of immune cell metabolism in ICH has gained attention, particularly the regulatory mechanisms of glycolytic reprogramming in neuroinflammation. This review explores how glycolysis activation in peripheral immune cells (including neutrophils, macrophages, T cells, and natural killer cells), central immune cells (microglia), and other glial cells (including astrocytes and oligodendrocytes) involved in immune regulation influences the inflammatory response following ICH. We analyze the metabolic shifts in glycolysis within these immune cells, highlighting its dual role in neuroinflammation: glycolysis not only provides rapid energy to immune cells, which can either promote or inhibit inflammation, but lactate—a glycolysis byproduct—can modulate inflammatory damage by altering pH and immune cell function. Furthermore, we explore the therapeutic potential of targeting glycolysis in immune cells for neuroinflammation treatment. A deeper understanding of the glycolytic mechanism in ICH may facilitate the development of clinical therapeutic strategies targeting metabolism.
{"title":"The role of immune cells glycolysis in neuroinflammation secondary to intracerebral hemorrhage","authors":"Baochun Luo , Sifan Liu , Lei Zheng , Baiwen Zhang , Yaxin Shang , Tong Shang , Jia Zheng , Binglin Kuang , Wei Zou","doi":"10.1016/j.clim.2025.110543","DOIUrl":"10.1016/j.clim.2025.110543","url":null,"abstract":"<div><div>Intracerebral hemorrhage (ICH) is the most lethal subtype of stroke, making the effective prevention and treatment of inflammatory secondary injury crucial. Recently, the role of immune cell metabolism in ICH has gained attention, particularly the regulatory mechanisms of glycolytic reprogramming in neuroinflammation. This review explores how glycolysis activation in peripheral immune cells (including neutrophils, macrophages, T cells, and natural killer cells), central immune cells (microglia), and other glial cells (including astrocytes and oligodendrocytes) involved in immune regulation influences the inflammatory response following ICH. We analyze the metabolic shifts in glycolysis within these immune cells, highlighting its dual role in neuroinflammation: glycolysis not only provides rapid energy to immune cells, which can either promote or inhibit inflammation, but lactate—a glycolysis byproduct—can modulate inflammatory damage by altering pH and immune cell function. Furthermore, we explore the therapeutic potential of targeting glycolysis in immune cells for neuroinflammation treatment. A deeper understanding of the glycolytic mechanism in ICH may facilitate the development of clinical therapeutic strategies targeting metabolism.</div></div>","PeriodicalId":10392,"journal":{"name":"Clinical immunology","volume":"279 ","pages":"Article 110543"},"PeriodicalIF":4.5,"publicationDate":"2025-06-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144279142","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-06-13DOI: 10.1016/j.clim.2025.110544
Siyuan Bu, Cong Ye, Shaozhe Cai, Lingli Dong
IKZF1 is a member of the Ikaros transcription factor family. It is involved in the regulation of the development and function of a variety of immune cells. Mutations or aberrant expression of IKZF1 are closely associated with the development of various immune-related diseases, including hematologic malignancies, solid tumors, and autoimmune diseases. In recent years, more and more studies have revealed the important role of IKZF1 in regulating immune responses, maintaining immune tolerance, and inhibiting the overactivation of immune cells. What's more, IKZF1 has been discovered to have a significant connection to the pathogenesis of autoimmune diseases. This review will summarize the role of IKZF1 in autoimmune diseases and its potential clinical applications.
{"title":"IKZF1: An important target for the treatment of autoimmune diseases","authors":"Siyuan Bu, Cong Ye, Shaozhe Cai, Lingli Dong","doi":"10.1016/j.clim.2025.110544","DOIUrl":"10.1016/j.clim.2025.110544","url":null,"abstract":"<div><div><em>IKZF1</em> is a member of the Ikaros transcription factor family. It is involved in the regulation of the development and function of a variety of immune cells. Mutations or aberrant expression of <em>IKZF1</em> are closely associated with the development of various immune-related diseases, including hematologic malignancies, solid tumors, and autoimmune diseases. In recent years, more and more studies have revealed the important role of <em>IKZF1</em> in regulating immune responses, maintaining immune tolerance, and inhibiting the overactivation of immune cells. What's more, <em>IKZF1</em> has been discovered to have a significant connection to the pathogenesis of autoimmune diseases. This review will summarize the role of <em>IKZF1</em> in autoimmune diseases and its potential clinical applications.</div></div>","PeriodicalId":10392,"journal":{"name":"Clinical immunology","volume":"279 ","pages":"Article 110544"},"PeriodicalIF":4.5,"publicationDate":"2025-06-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144298556","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
扫码关注我们
求助内容：
应助结果提醒方式：
京公网安备 11010802042870号