Immunologic Research最新文献

{"title":"Therapeutic potential of extracellular vesicles in systemic lupus erythematosus: a systematic review.","authors":"Renata Vaz Voltareli, Nayara Rozalem Moretti, Giovanni Garrido Puci, Graziela Garrido Mori","doi":"10.1007/s12026-025-09680-z","DOIUrl":"10.1007/s12026-025-09680-z","url":null,"abstract":"<p><p>Current therapies for Systemic lupus erythematosus (SLE), such as immunosuppressants and glucocorticoids, are associated with significant side effects, necessitating alternative treatment approaches. Extracellular vesicles (EVs) have emerged as a potential therapeutic option due to their immunomodulatory properties and ability to regulate innate and adaptive immune responses. Thus, the objective of the present study was to systematically analyze the therapeutic potential of EVs for treating SLE. A systematic review was conducted according to PRISMA guidelines. An electronic search was performed in the PubMed/ MEDLINE, Scopus, Cochrane Library and Open Gray databases covering the period up to September 2024 to respond to the PICO answer \"Would EVs have therapeutic potential in SLE?\" Control of Systemic lupus erythematosus progression and the cellular and molecular mechanisms present were considered the primary and secondary outcome, respectively. The bias risk of studies was evaluated by SYRCLE's RoB. A total of 7 studies met the inclusion criteria, and the data exhibited that EVs reduced disease severity, improved survival rates and ameliorated organ-specific damage in SLE models. It was seen that EVs reduction of autoantibody, Th17 and Tfh cells, type-1 macrophage, neutrophils and pro-inflammatory cytokines, alongside an increase in Tregs, immunosuppressive cytokines and type-2 macrophage. The studies showed high scientific evidence. EV therapy exhibits potential in mitigating SLE progression by modulating immune responses and reducing inflammation. Further research is required to confirm these datas in humans, facilitating advancement for future clinical applications.</p>","PeriodicalId":13389,"journal":{"name":"Immunologic Research","volume":"73 1","pages":"120"},"PeriodicalIF":3.1,"publicationDate":"2025-08-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144855127","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"GFAP as a marker of astrocytic damage correlated with medication overuse in migraine.","authors":"Sara Carta, Vanessa Chiodega, Riccardo Tiberi, Alessia Pasquali, Sergio Ferrari, Silvia Bozzetti, Federico Ranieri, Fabio Marchioretto, Sara Mariotto","doi":"10.1007/s12026-025-09674-x","DOIUrl":"10.1007/s12026-025-09674-x","url":null,"abstract":"<p><p>Different mechanisms are involved in migraine pathogenesis, including neurogenic inflammation, neurodegenerative processes, and a potential role of microglia. The aim of this study was to assess axonal and glial damage measuring serum levels of neurofilament light chain (NfL) and glial fibrillary acidic protein (GFAP) in migraine patients. Serum samples of 25 patients with episodic migraine (EM), 25 with chronic migraine (CM) diagnosed in accordance with the International Classification of Headache Disorders, 3rd edition (ICHD-3), and 50 age-matched healthy controls were prospectively collected. NfL and GFAP levels were assessed using ultrasensitive paramagnetic bead-based ELISA (SIMOA). Non-parametric tests were used for group comparison and 2-tailed Spearman analysis to assess correlations. GFAP levels were significantly increased in migraine patients (median 103.15 pg/mL [IQR 70.98-146.34] vs. 69.43 pg/mL [IQR 53.04-91.85], p < 0.001), particularly in those with medication overuse (106.08 [IQR 87.94-159.07] vs. 71.38 [IQR 54.16-135.06], p = 0.007), without difference between EM and CM (p = 0.985). Although NfL levels were not increased (p = 0.387), they were higher in patients with a long migraine course (rho 0.519, p < 0.001). Attack at sampling/days from last attack, migraine frequency/attack severity did not influence NfL or GFAP levels. Our findings demonstrate the occurrence of glial damage, particularly correlated with medication overuse, and the presence of axonal damage in the later disease stage, providing potential novel cues for the migraine pathogenesis.</p>","PeriodicalId":13389,"journal":{"name":"Immunologic Research","volume":"73 1","pages":"119"},"PeriodicalIF":3.1,"publicationDate":"2025-08-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12334492/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144804005","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"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 CD40L-expressing CXCR5⁺CD8⁺ follicular cytotoxic T cells in chronic lymphocytic leukemia.","authors":"Fatih Akboga, Fehmi Hindilerden, Ipek Yonal Hindilerden, Emine Gulturk, Gunnur Deniz, Metin Yusuf Gelmez","doi":"10.1007/s12026-025-09672-z","DOIUrl":"10.1007/s12026-025-09672-z","url":null,"abstract":"<p><p>A newly identified cell subset within CD8⁺T cells expressing CXCR5 of follicular cytotoxic T cells (T_FC) lyse the infected or tumor cells. Recent studies have suggested that some T_FC cell subsets may be involved in the regulation of antibody responses. We aimed to determine the subset of T_FC which differentiates in patients diagnosed with chronic lymphocytic leukemia (CLL) and their role in CLL immunopathogenesis. The peripheral blood mononuclear cells were isolated from 29 CLL patients and 19 healthy subjects. Intracellular IL-4, IL-17, IL-21, IFN-γ, perforin, and granzyme-B levels were investigated in T_FC subsets. Increased levels of IL-4, IL-17, IL-21, IFN-γ and perforin, and decreased granzyme B expression levels were observed in CD40L⁺T_FC cells compared to the levels in CD40L^-T_FC cells in the analysis of healthy individuals. T_FC and its subsets were analyzed in CLL patients and healthy individuals, T_FC and CD40L⁺T_FC cells were increased in CLL patients and there was a positive correlation between T_FC and CD5⁺CD19⁺ cells. Moreover, increased number of T_FC cells were detected in CLL patients with more progressive disease. Higher expression level of IL-4, IL-17, IL-21, and IFN-γ was observed in CD40L⁺T_FC cells of patients compared to the levels in healthy controls. Our findings might indicate that CD40L⁺T_FC cells may have a B cell activating role rather than exhibiting a cytotoxic role. Considering the effects of CD40L⁺T_FC cells on B cells, determining subsets of T_FC cells which differentiate and understanding the functions of these subsets is crucial to elucidate their roles in the pathogenesis of B cell malignancies.</p>","PeriodicalId":13389,"journal":{"name":"Immunologic Research","volume":"73 1","pages":"118"},"PeriodicalIF":3.1,"publicationDate":"2025-08-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144788854","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Immunoglobulin G4-related sclerosing mastitis: MRI findings and the literature review.","authors":"Lishan Wang, Fan Yang, Xiaoyan Hu, Na Li, Jie Gou, Wei Lin, Shengjian Zhang","doi":"10.1007/s12026-025-09668-9","DOIUrl":"10.1007/s12026-025-09668-9","url":null,"abstract":"<p><p>Immunoglobulin G4-related disease (IgG4-RD) is a rare immune-mediated fibro-inflammatory condition that can affect nearly any organ, with breast involvement (IgG4-related sclerosing mastitis, IgG4-RM) being exceptionally uncommon. This disease primarily affects middle-aged to elderly women and is frequently misdiagnosed as malignancy due to non-specific clinical and imaging features. We report a case of a 44-year-old woman with a painless right breast mass showing hypoechoic ultrasound findings and magnetic resonance imaging (MRI) characteristics, including a high ADC value and homogeneous enhancement with a persistent time-intensity curve (TIC). Histopathology confirmed IgG4-RM, with no recurrence after 12 months. A review of 24 published lectures highlights the diagnostic challenges and imaging variability of IgG4-RM.</p>","PeriodicalId":13389,"journal":{"name":"Immunologic Research","volume":"73 1","pages":"117"},"PeriodicalIF":3.1,"publicationDate":"2025-08-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144784236","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Effects of belimumab on peripheral blood Breg cells and cytokines in childhood systemic lupus erythematosus.","authors":"Qianqian Peng, Ruifeng Zhang, Shan Qiu, Tingting Yuan, Juan Lv, Na Chen, Qian Lu, Zhaowen Zhong","doi":"10.1007/s12026-025-09673-y","DOIUrl":"10.1007/s12026-025-09673-y","url":null,"abstract":"<p><p>To evaluate the therapeutic effectiveness of belimumab (BLM) in childhood systemic lupus erythematosus (cSLE) by analyzing peripheral blood Breg cell subsets and related cytokines at multiple time points post-treatment, compared with conventional therapy. From January 2023 to August 2023, 36 cSLE patients receiving BLM plus standard therapy (BLM group) and 35 receiving standard therapy alone (conventional group) were enrolled. Thirty age- and sex-matched healthy children were included as controls. Flow cytometry was used to detect absolute counts and ratios of peripheral Breg cell subsets at baseline, 6 weeks, 6 months, and 1 year. Serum cytokine levels (IL-2, IL-10, IL-21, IL-35, and IFN-γ) were measured by ELISA. After 6 weeks, IL-2, IL-21, and IFN-γ levels decreased significantly in both groups (P > 0.05 between groups); however, after 6 months and 1 year, these cytokines remained lower in the BLM group (all P < 0.05). IL-10 and IL-35 levels increased in both groups from week 6, with a milder increase in the BLM group (all P < 0.05). CD3⁻CD19⁺ B cells declined in both groups, with significant intergroup differences (P < 0.001). The BLM group showed a higher proportion of CD27⁺CD24⁺ B cells at week 6 compared to the conventional group (P < 0.05), but this reversed at 1 year (P < 0.05). CD38⁺CD24⁺ B cells were significantly higher in the BLM group at 6 months and 1 year (P < 0.001), while the conventional group showed no significant change after 6 weeks (P > 0.05). At baseline, the relative proportion of CD38⁺CD19⁺ B cells was higher in the BLM group than in the conventional treatment group (all P < 0.05). With ongoing treatment, both groups showed a decreasing trend in B cell proportions, with statistically significant differences observed within each group (all P < 0.05). Moreover, the decline in the BLM group was more pronounced compared to the conventional group at corresponding time points (all P < 0.05). Belimumab may exert immunomodulatory effects in childhood systemic lupus erythematosus by influencing peripheral Breg cell subsets and cytokine profiles. Compared with conventional therapy, it appears to provide more sustained regulation of certain immune parameters over time. These findings suggest its potential as a complementary therapeutic option targeting B cell dysregulation in cSLE, although further studies are needed to confirm these observations and clarify the underlying mechanisms.</p>","PeriodicalId":13389,"journal":{"name":"Immunologic Research","volume":"73 1","pages":"116"},"PeriodicalIF":3.1,"publicationDate":"2025-08-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12325528/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144784235","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"SOCS1 improves abnormal IgA galactosylation in IgA nephropathy by regulating the TLR9/MyD88 pathway.","authors":"Yanru Huang, Qinghai Wang, Chunqin Lin, Bingbing Qiu, Shulian Chen, Jianxin Wang","doi":"10.1007/s12026-025-09669-8","DOIUrl":"https://doi.org/10.1007/s12026-025-09669-8","url":null,"abstract":"<p><p>Abnormal galactosylation of IgA is a core factor in the development of IgA nephropathy (IgAN). Suppressor of cytokine signaling 1 (SOCS1) expression negatively correlates with IgA1 secretion in IgAN patients and that TLR9/MyD88 promotes aberrantly glycosylated IgA formation. Therefore, the present study exposed whether SOCS1 is involved in aberrant galactosylation of IgA in IgAN by regulating the TLR9/MyD88 signaling pathway through in vivo and in vitro experiments. Differential expression of SOSC1 in IgAN patients and non-IgAN patients was analyzed using bioinformatics analysis and immunofluorescence. The IgAN mouse model and the IgA1-secreting DAKIKI cell model were used to validate the effect of SOCS1 on aberrant IgA galactosylation in IgAN. In addition, qRT-PCR, western blot, and immunohistochemistry experiments were performed to reveal the regulation of the TLR9/MyD88 pathway by SOCS1 in IgAN. The expression of SOCS1 was suppressed in renal tissues and peripheral blood mononuclear cells (PBMC) of IgAN patients, consistent with the results of dataset GSE35487. The expression of C1GALT1 in PBMC from IgAN patients was decreased and positively correlated with SOCS1 expression, while the expressions of TLR9 and MyD88 were increased and negatively correlated with SOCS1 expression. In vitro, SOCS1 overexpression inhibited the secretion of IgA1 and galactose-deficient IgA1 (Gd-IgA1) in DAKIKI cells, as well as the expression of TLR9. Knockdown of SOCS1 had the opposite effect. As a negative regulator of TLR9, SOCS1 inhibited the expression of TLR9, thereby preventing aberrant IgA galactosylation. MyD88 knockdown restored the CpG-ODN (TLR9 ligand)-induced overproduction of IgA1 and Gd-IgA1, and the reduction of C1GALT1. In vivo experiments demonstrated that SOCS1 significantly inhibited the production of aberrant glycosylated IgA IgG-IgA immune complexes and IL-6 in mice, reduced glomerular IgA, IgG, and C3 deposition and tethered cell proliferation, and alleviated renal injury. Decreased expression of SOCS1 contributes to IgAN pathogenesis by promoting aberrant IgA galactosylation via activating TLR9/MyD88 pathway. Our study may provide a prospective treatment target for IgAN.</p>","PeriodicalId":13389,"journal":{"name":"Immunologic Research","volume":"73 1","pages":"115"},"PeriodicalIF":3.1,"publicationDate":"2025-08-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144784237","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Exploring the role of the Th9/IL-9 axis in atopic dermatitis: analysis of Th9 cells, PU.1 expression and serum IL-9 levels.","authors":"Tabasum Shafi, Roohi Rasool, Rubeena Bhat, Sakeena Ayub, Ayaz Gull, Ishfaq Rashid, Aabid M Koul","doi":"10.1007/s12026-025-09671-0","DOIUrl":"https://doi.org/10.1007/s12026-025-09671-0","url":null,"abstract":"<p><p>Atopic dermatitis (AD) is a chronic inflammatory skin disease resulting from complex interactions between genetic, environmental, and immunological factors, particularly the dysregulation of T helper (Th) cell subsets. While Th2 responses have been central to AD research, evidence highlights the role of Th9 cells and their signature cytokine, interleukin-9 (IL-9), in allergic inflammation. However, the involvement of the Th9/IL-9 axis in AD remains insufficiently characterized. This study investigates the role of the Th9/IL-9 axis in AD through an integrated clinical, immunological, and molecular approach. The study comprised a total of 89 subjects, consisting of 54 AD cases and 35 healthy controls. Disease severity and allergen sensitivity were assessed using SCORAD scores and skin prick testing, respectively. PU-1 mRNA was quantified using real-time PCR. Th9 cell frequency was determined through flow cytometry, vitamin D levels were measured by chemiluminescence, and total IgE and IL-9 levels were estimated using ELISA. AD patients demonstrated a significant increase in circulating Th9 cell frequency (11.5 ± 0.3% vs. 5.0 ± 0.5%, p < 0.0001), PU.1 mRNA expression with an average 2.5-fold upregulation (p < 0.001), and elevated serum IL-9 concentrations (18.6 ± 6.3 pg/mL vs. 8.3 ± 1.9 pg/mL, p < 0.0001) compared to healthy controls. Stratified analysis revealed significant associations of PU.1 mRNA and IL-9 levels with rural residence, vitamin D deficiency, and peripheral eosinophilia (p < 0.05). Allergen sensitivity, as determined by skin prick testing, was positive in 50% of AD patients, and 66.7% exhibited elevated total serum IgE levels. Our findings underscore the involvement of the Th9/PU.1/IL-9 axis in the immunopathogenesis of AD. The observed upregulation of Th9 cell frequency, PU.1 expression, and IL-9 levels suggests a contributory role of Th9-mediated pathways in disease development and severity. These results provide a foundation for future studies investigating the dynamic crosstalk between Th9 cells, other immune cell subsets, and epidermal components, with the aim of identifying novel immunomodulatory targets for precision therapy in AD.</p>","PeriodicalId":13389,"journal":{"name":"Immunologic Research","volume":"73 1","pages":"114"},"PeriodicalIF":3.1,"publicationDate":"2025-07-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144753235","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Severe interstitial lung disease as the first manifestation of a STING1 variant in a familial case.","authors":"Zhijuan Kang, Ruqian Fu, Zhihui Li, Liang Zhang","doi":"10.1007/s12026-025-09670-1","DOIUrl":"https://doi.org/10.1007/s12026-025-09670-1","url":null,"abstract":"<p><p>STING-associated vasculopathy with onset in infancy (SAVI) is a very rare autosomal-dominant Mendelian autoinflammatory disease caused by heterozygous gain-of-function mutations in STING1. Reported carriers of a STING1 gain-of-function mutations are mostly symptomatic. Herein, we present a case study of an infant who presented with cyanosis, dyspnea, clubbing fingers, failure to thrive, and widespread interstitial changes, all consistent with interstitial lung disease (ILD); however, there was a notable lack of characteristic cutaneous features and recurrent fever. Whole-exome sequencing detected a pathogenic heterozygous mutation (p.Arg218Gln) in STING1. Intriguingly, this mutation was also present in her father (aged 32 years), whereas this carrier was healthy and without clinical symptoms. This study emphasizes the need to consider the possibility of SAVI in infants with ILD, even if they lack typical manifestations. Our study also underlines the possibility that carriers with STING gain-of-function mutations are clinically asymptomatic.</p>","PeriodicalId":13389,"journal":{"name":"Immunologic Research","volume":"73 1","pages":"113"},"PeriodicalIF":3.1,"publicationDate":"2025-07-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144742061","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"SPP1 + macrophages facilitate pancreatic cancer progression via ITGB6-mediated interactions: evidence from integrated multi-omics analysis and experimental validation.","authors":"Jiachen Ge, Jianping Cai, Gaolei Zhang, Deyu Li, Lianyuan Tao","doi":"10.1007/s12026-025-09666-x","DOIUrl":"10.1007/s12026-025-09666-x","url":null,"abstract":"<p><p>Basement membranes (BMs) and tumor-associated macrophages (TAMs) are crucial stromal components in pancreatic cancer (PC), critically influencing disease progression. Bulk and single-cell RNA-seq (scRNA-seq) data were acquired from publicly available databases. Through integration of multiple machine learning algorithms, we developed and validated a BM-related subtype and prognostic signature in PC cohorts. The expression profiles of BM-related genes in PC were verified using experimental approaches. We further investigated the functional mechanisms of a core gene in PC progression. Additionally, we characterized the TAM landscape in PC, revealing distinct TAM subsets associated with tumor progression and their dynamic interactions with BM components. Based on BM-related gene expression profiles, PC samples were stratified into two distinct subtypes. Our integrated prognostic signature combining LASSO and survival-SVM algorithms demonstrated robust performance in predicting PC outcomes and clinical characteristics. LAMA3, ITGA3, and ITGB6 showed higher expression in PC specimens versus normal controls. Functional experiments confirmed that ITGB6 knockdown markedly suppressed PC progression. Through integrative analysis of multiple scRNA-seq datasets of PC, we established a single-cell landscape of TAMs and ductal cells, respectively. SPP1 + TAMs correlated with poor PC prognosis and facilitated tumor progression through ITGB6-mediated interactions. In this study, we established novel PC subtypes and constructed a prognostic signature based on BM-related genes. An atlas of TAMs was constructed in PC. SPP1 + macrophages drove pancreatic cancer progression via ITGB6-mediated interactions.</p>","PeriodicalId":13389,"journal":{"name":"Immunologic Research","volume":"73 1","pages":"112"},"PeriodicalIF":3.1,"publicationDate":"2025-07-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144730093","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Molecular mechanisms and treatment strategies for discogenic lumbar pain.","authors":"Sumin Yan, Bingqiu Han, Chao Song, Limin Yan","doi":"10.1007/s12026-025-09667-w","DOIUrl":"10.1007/s12026-025-09667-w","url":null,"abstract":"<p><p>Discogenic low back pain (DLBP) is one of the main causes of chronic low back pain, and its core pathological mechanism is due to various molecular changes caused by intervertebral disc degeneration. The normal intervertebral disc is composed of the nucleus pulposus, annulus fibrosus, and cartilaginous endplate, and has structural characteristics without blood vessels or nerves, relying on dispersed support to maintain homeostasis. During the process of degeneration, nucleus pulposus cells undergo apoptosis and cell senescence, its synthesis ability decreases, and the balance of extracellular matrix (ECM) is disrupted. Meanwhile, inflammatory factors such as IL-1β and TNF-α are continuously upregulated, activating pathways such as NF-κB and MAPK, inducing the expression of MMPs and ADAMTS, and accelerating ECM degradation. Matrix disruption further promotes the release of neurotrophic factors (such as NGF, VEGF), induces angiogenesis and nerve fiber invasion into the nucleus pulposus area, destroys the immune barrier, and leads to peripheral nerve sensitization. The central system mediates central remodeling through factors such as BDNF and CGRP, maintaining and amplifying pain signals. This article systematically summarizes the molecular mechanism of DLBP and summarizes relevant treatment strategies based on it, including conservative treatments such as NSAIDs, interventional methods such as radiofrequency ablation and fusion, as well as emerging therapies such as targeted anti-inflammatory, anti-neurogenic, matrix protection, and stem cell regeneration. The aim is to provide theoretical support and research directions for personalized treatment and mechanism interventions of DLBP.</p>","PeriodicalId":13389,"journal":{"name":"Immunologic Research","volume":"73 1","pages":"111"},"PeriodicalIF":3.1,"publicationDate":"2025-07-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144717855","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}