Frontiers in Immunology最新文献

{"title":"Lactate-mediated metabolic reprogramming of tumor-associated macrophages: implications for tumor progression and therapeutic potential.","authors":"Xiaohan Jin, Ni Zhang, Tinghao Yan, Jingyang Wei, Lingli Hao, Changgang Sun, Haibo Zhao, Shulong Jiang","doi":"10.3389/fimmu.2025.1573039","DOIUrl":"10.3389/fimmu.2025.1573039","url":null,"abstract":"<p><p>The tumor microenvironment (TME) is characterized by distinct metabolic adaptations that not only drive tumor progression but also profoundly influence immune responses. Among these adaptations, lactate, a key metabolic byproduct of aerobic glycolysis, accumulates in the TME and plays a pivotal role in regulating cellular metabolism and immune cell function. Tumor-associated macrophages (TAMs), known for their remarkable functional plasticity, serve as critical regulators of the immune microenvironment and tumor progression. Lactate modulates TAM polarization by influencing the M1/M2 phenotypic balance through diverse signaling pathways, while simultaneously driving metabolic reprogramming. Furthermore, lactate-mediated histone and protein lactylation reshapes TAM gene expression, reinforcing their immunosuppressive properties. From a therapeutic perspective, targeting lactate metabolism has shown promise in reprogramming TAMs and enhancing anti-tumor immunity. Combining these metabolic interventions with immunotherapies may further augment treatment efficacy. This review underscores the crucial role of lactate in TAM regulation and tumor progression, highlighting its potential as a promising therapeutic target in cancer treatment.</p>","PeriodicalId":12622,"journal":{"name":"Frontiers in Immunology","volume":"16 ","pages":"1573039"},"PeriodicalIF":5.7,"publicationDate":"2025-05-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12106438/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144157888","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":"Factors associated with persistent anti-desmoglein positivity after remission in pemphigus vulgaris: a prospective registry-based cohort study.","authors":"Yuxi Zhou, Yiyi Wang, Mi Wang, Xingli Zhou, Limei Luo, Wei Yan, Wei Li","doi":"10.3389/fimmu.2025.1557556","DOIUrl":"10.3389/fimmu.2025.1557556","url":null,"abstract":"<p><strong>Introduction: </strong>Anti-desmoglein (Dsg) antibodies are well-established markers correlated with clinical phenotype and disease severity in pemphigus vulgaris (PV). However, elevated anti-Dsg antibody levels have been observed in some patients during clinical remission (CR). This study aimed to identify clinical characteristics and risk factors in PV patients with elevated anti-Dsg antibodies after achieving CR.</p><p><strong>Methods: </strong>We conducted a cohort study based on the prospective registry database of autoimmune bullous diseases patients at West China Hospital between April 2016 and March 2022. PV patients with at least 12 months of follow-up were enrolled. The pemphigus disease area index (PDAI) and anti-Dsg antibody titers were measured at baseline and 1, 3, 6, 9, 12 months during follow-up. Univariate, multivariate analyses and receiver operating characteristics (ROC) curves were performed to identify associated factors with persistent antibody positivity and optimal cut-off values respectively. The primary outcome was the persistent positivity of antibodies against Dsg after achieving CR.</p><p><strong>Results: </strong>Among 239 PV patients enrolled in this study, 118 (49%) achieved CR. Cataracts were identified as an independent risk factor for persistent anti-Dsg1 positivity after CR. Higher baseline anti-Dsg3 antibody titers and PDAI scores were significant predictors of increased anti-Dsg3 levels post-CR, with gender also being a contributing factor. ROC analysis determined a cut-off value of 157.4 U/mL for anti-Dsg3 with 56.3% sensitivity and 82.6% specificity.</p><p><strong>Conclusion: </strong>The presence of Cataracts may indicate persistent anti-Dsg1 positivity after CR, while elevated anti-Dsg3 titers and PDAI scores at baseline may predict sustained elevated anti-Dsg3 post-CR.</p>","PeriodicalId":12622,"journal":{"name":"Frontiers in Immunology","volume":"16 ","pages":"1557556"},"PeriodicalIF":5.7,"publicationDate":"2025-05-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12106514/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144157952","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":"Gene expression profiling in pure neural leprosy: insights into pathogenesis and diagnostic biomarkers.","authors":"Mariana Martins de Athaide, Thyago Leal-Calvo, Tatiana Pereira Da Silva, Thabatta Leal Silveira Andrezo Rosa, Helen Ferreira, Bernardo Miguel de Oliveira Pascarelli, Ana Caroline Siquara de Sousa, Marcia Rodrigues Jardim, Roberta Olmo Pinheiro","doi":"10.3389/fimmu.2025.1550687","DOIUrl":"10.3389/fimmu.2025.1550687","url":null,"abstract":"<p><strong>Introduction: </strong>Leprosy may affect skin and nerves, leading to permanent disabilities and deformities. Pure neural leprosy (PNL) lacks skin lesions, complicating diagnosis. Moreover there is no a specific treatment to control neural damage. Transcriptomic profiling may reveals unique gene expression changes in PNL nerves, shedding light on immune response and pathogenesis. These findings may guide early diagnosis and improve patient outcome.</p><p><strong>Methods: </strong>In the present study, we investigated the gene profiling of nerve samples from patients with PNL and revealed significant transcriptomic alterations compared to non-leprosy controls.</p><p><strong>Results: </strong>Principal Component Analysis (PCA) of the 500 most differentially expressed genes separated the groups, with 1,199 genes showing differential expression (|log₂FC| ≥ 1, FDR ≤ 0.1). Downregulated genes included <i>GAS2L2</i>, <i>TRIM67</i>, <i>IL1RAPL1</i>, <i>MAP1LC3B2</i>, and <i>NTNG1</i>, implicated in neuronal development and autophagy, while upregulated genes were linked to immune responses. Functional analyses highlighted inflammasome activation and autophagy impairment in PNL, correlating with nerve inflammation and architecture loss.</p><p><strong>Discussion: </strong>We hope that our data will aid in identifying new markers, fostering strategies for early diagnosis, preventing disabilities, and improving the management of PNL patients.</p>","PeriodicalId":12622,"journal":{"name":"Frontiers in Immunology","volume":"16 ","pages":"1550687"},"PeriodicalIF":5.7,"publicationDate":"2025-05-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12104059/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144150175","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":"Case Report: IgG4-RD-related ophthalmopathy combined with monoclonal gammopathy of undetermined significance.","authors":"Shanshan Liang, Wei Xu, Peiying Zhong, Chuanmin Tao, Li Zhang, Chengyao Jia","doi":"10.3389/fimmu.2025.1565388","DOIUrl":"10.3389/fimmu.2025.1565388","url":null,"abstract":"<p><p>IgG4-related disease (IgG4-RD), an immune-mediated fibroinflammatory disorder, has few reports in combination with monoclonal gammopathy of undetermined significance (MGUS). Herein, we present a case of a 69-year-old woman with manifestations of left orbital occupation and visual acuity decline. Ancillary tests indicated persistent positivity of IgG4 antibody, and IgG4-RD-related ophthalmopathy was diagnosed based on the criteria. Concurrently, serum protein electrophoresis revealed an M protein level of 12.23 g/L. Immunofixation electrophoresis suggested a positive IgG λ-type M protein, and MGUS was diagnosed in conjunction with bone marrow smear and flow cytometry.</p>","PeriodicalId":12622,"journal":{"name":"Frontiers in Immunology","volume":"16 ","pages":"1565388"},"PeriodicalIF":5.7,"publicationDate":"2025-05-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12104068/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144150262","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":"MicroRNA expression and their molecular targets in food allergies: a systematic review.","authors":"Tekan Singh Rana, Rishipal Rastrapal Bansode, Jenny Pakhrin Rana, Leonard L Williams","doi":"10.3389/fimmu.2025.1524392","DOIUrl":"10.3389/fimmu.2025.1524392","url":null,"abstract":"<p><strong>Introduction: </strong>MicroRNAs (miRs) play an essential role in adaptive and innate immune systems by regulating the development of immune cells. However, detailed studies of miRs' role in food allergies are scarce compared to those of other allergic or non- allergic diseases. This systematic review aims to study miRs expression and its role in food allergies (FAs) and determine the signature miRs in FAs.</p><p><strong>Method: </strong>Research articles published since 2015 were selected from various databases: Scopus, PubMed, ScienceDirect, and Web of Science. Randomized clinical trials, observational clinical studies, and <i>in vivo</i> studies were assessed via the Cochrane Risk of Bias 2 tool, the Newcastle-Ottawa scale, and SYRCLE method, respectively. The characteristics of the included studies, population characteristics, and experimental details were extracted, and the data were synthesized narratively.</p><p><strong>Result: </strong>MiRs expression had been investigated in the context of cow milk allergy (CMA) and peanut allergy (PA) through both <i>in vivo</i> studies and clinical trials. Clinical trials included allergies to multiple combined foods, individual foods (such as milk, peanut, and what), and drugs and venom, while <i>in vivo</i> studies were conducted on milk, egg, and peanut allergies. MiR-146a, miR- 155, and miR-30a-5p were common miRs between <i>in vivo</i> studies and clinical trials. Moreover, few miRs were commonly studied between different types of food allergies. In clinical trials, miR-143-3p was studied in peanut allergy and non-celiac wheat sensitivity (NCWS), and miR-155 was studied in CMA and egg allergy in <i>in vivo</i> studies. Furthermore, the same miRs varied on their molecular target and effect depending on the type of food allergy.</p><p><strong>Discussion: </strong>The study on signature miRs and their molecular target determination for the therapeutic purpose of food allergy is in its initial stage. For individual food allergies, miRs determination via next-generation sequencing (NGS), their validation via polymerase chain reaction (PCR), and target molecule determination via RNA interference (RNAi) should be the focus of future studies in order to determine reliable signature miRs of food allergy.</p>","PeriodicalId":12622,"journal":{"name":"Frontiers in Immunology","volume":"16 ","pages":"1524392"},"PeriodicalIF":5.7,"publicationDate":"2025-05-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12104090/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144150205","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":"Underestimated virus impaired cognition-more evidence and more work to do.","authors":"Maher Un Nisa Awan, Faisal Mahmood, Xiao-Bin Peng, Fenshuang Zheng, Jun Xu","doi":"10.3389/fimmu.2025.1550179","DOIUrl":"10.3389/fimmu.2025.1550179","url":null,"abstract":"<p><p>Neurodegenerative disorders (NDs) are chronic neurological diseases that can be of idiopathic, genetic, or potentially infectious origin. Although the exact cause of neurodegeneration is unknown, it might be result of a confluence of age, genetic susceptibility factors, and environmental stresses. The blood-brain barrier shields the brain from the majority of viral infections, however neurotropic viruses are able to breach this barrier and infect central nervous system. Growing research points to a possible connection between viruses and neurodegenerative diseases, indicating that virus-induced neuroinflammation and disruption of neuronal protein quality control may play a role in the initial stages of disease progression. The diagnosis and treatment of NDs are urgent and challenging. Even though there is limited clinical evidence to support the use of antiviral medications and their dose regimens within the central nervous system (CNS), with the exception of acyclovir, they are currently utilized to treat various viral CNS infections. Understanding the neuropathogenesis of viral CNS infection may help with targeted diagnosis and treatment plans by focusing on the molecular mechanisms of the CNS. It may also be helpful in the search for new antiviral drugs, which are crucial for better managing these neurotropic viral infections. This review focuses on new findings linking viral infection to NDs and explores how viral modifications of cellular functions can impact the development of neurodegeneration and will also explore the therapeutic potential of antiviral drugs in NDs.</p>","PeriodicalId":12622,"journal":{"name":"Frontiers in Immunology","volume":"16 ","pages":"1550179"},"PeriodicalIF":5.7,"publicationDate":"2025-05-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12104254/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144150254","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":"NKG2D triggering hampers DNAM-1-mediated signaling in human NK cells.","authors":"Caterina Marangio, Nadia Domenica Milito, Erisa Putro, Alessia Carnevale, Cristina Capuano, Alessandra Zingoni, Marco Cippitelli, Angela Santoni, Rossella Paolini, Rosa Molfetta","doi":"10.3389/fimmu.2025.1575059","DOIUrl":"10.3389/fimmu.2025.1575059","url":null,"abstract":"<p><strong>Introduction: </strong>Natural Killer (NK) cells are cytotoxic innate lymphocytes able to detect transformed cells through the balanced action of inhibitory and activating receptors. NKG2D is one of the main activating receptors involved in tumor surveillance thanks to its ability to recognize stress-induced ligands. Of note, the prolonged exposure to NKG2D ligands promotes receptor down-modulation that results in defective activation of NKG2D and other unrelated activating receptors, including DNAM-1 that is also involved in tumor clearance. However, further investigations are necessary to characterize how the NKG2D/DNAM-1 interplay affects NK cell anti-tumor function.</p><p><strong>Methods: </strong>Primary cultured human NK cells were stimulated with the natural ligand MICA or an anti-NKG2D agonist antibody. The expression of activating and inhibitory receptors as well as DNAM-1-triggered signaling events and cytotoxicity were evaluated by flow cytometry. DNAM-1-mediated granule polarization was evaluated by confocal microscopy.</p><p><strong>Results: </strong>We showed that NKG2D crosslinking mediated by the natural ligand MICA or an agonist antibody had different consequences on primary cultured human NK cells. Indeed, MICA stimulation increases the expression of the checkpoint receptor TIGIT that is able to counteract DNAM-1 activation. Stimulation with the agonist antibody, without altering TIGIT expression, directly inhibits DNAM-1-mediated signal transduction and cytotoxic function with a mechanism that required NKG2D endocytosis.</p><p><strong>Discussion: </strong>Our findings contribute to shed light on the functional consequences of NKG2D engagement, demonstrating that a direct impact on DNAM-1-mediated signal transduction occurs independently from the modality of NKG2D crosslinking. Understanding the molecular mechanisms responsible for suppression of NK cell activation may help the development of therapeutic anti-cancer strategies aimed to prevent NK cell dysfunction or to reinvigorate an impaired cytotoxic activity.</p>","PeriodicalId":12622,"journal":{"name":"Frontiers in Immunology","volume":"16 ","pages":"1575059"},"PeriodicalIF":5.7,"publicationDate":"2025-05-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12104298/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144150211","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":"Steroid hormones and influence of therapeutic drugs in Chinese postmenopausal rheumatoid arthritis patients.","authors":"Ying-Ying Zhang, Na Yang, Hua-Yong Zhang, Jia-Jia Ge, Si-Min Yan, Dan Han, Qian-Ye Qiu, Wei-Hong Ge, Qing Shu","doi":"10.3389/fimmu.2025.1589798","DOIUrl":"10.3389/fimmu.2025.1589798","url":null,"abstract":"<p><strong>Objective: </strong>To investigate steroid hormone profiles and therapeutic modulation in Chinese postmenopausal rheumatoid arthritis (RA) patients.</p><p><strong>Methods: </strong>This cross-sectional study enrolled 138 postmenopausal women, including 88 RA patients stratified by treatment status (23 treatment-naïve, 35 on methotrexate [MTX] monotherapy, and 30 receiving MTX plus glucocorticoids [GC]) and 50 age-matched healthy controls. Using liquid chromatography-tandem mass spectrometry (LC-MS/MS), we quantified 36 steroid hormones/metabolites to assess treatment-associated endocrine alterations. Group comparisons employed non-parametric Kruskal-Wallis test for multi-group comparisons, with <i>post-hoc</i> Mann-Whitney U tests and false discovery rate (FDR) correction for multiple comparisons. Statistical significance was defined as p<0.05 after FDR correction.</p><p><strong>Results: </strong>Untreated RA patients demonstrated significant global steroid dysregulation, characterized by marked suppression of multiple adrenal steroids (including aldosterone, cortisol, and testosterone) compared to healthy controls (all FDR<0.05). This was accompanied by profound alterations in estrogen metabolism, notably a hyperactivated 2-hydroxylation pathway and depleted 16-hydroxylation metabolites (FDR<0.001). MTX treatment partially restored steroid homeostasis, significantly improving aldosterone and androgen profiles (FDR<0.05) toward levels observed in healthy controls. However, the addition of GC therapy further disrupted endocrine balance, significantly suppressing cortisol, testosterone, and total estrogens (FDR<0.05), while pathologically amplifying the 4-hydroxylation pathway (FDR<0.001), a process potentially linked to synovial inflammation.</p><p><strong>Conclusions: </strong>This study demonstrates that impaired steroidogenesis and estrogen pathway dysregulation are characteristic features of postmenopausal RA, with MTX showing unexpected hormone-restorative effects. While GC therapy provides symptomatic relief, it paradoxically exacerbates endocrine disruption, suggesting the need for personalized hormonal monitoring in long-term GC-treated patients.</p>","PeriodicalId":12622,"journal":{"name":"Frontiers in Immunology","volume":"16 ","pages":"1589798"},"PeriodicalIF":5.7,"publicationDate":"2025-05-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12104170/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144150252","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":"Co-administration of vitamin D and N-acetylcysteine to modulate immunosenescence in older adults with vitamin D deficiency: a randomized clinical trial.","authors":"Samira Rastgoo, Katayoun Pourvali, Seyed Ahmad Raeissadat, Ghazaleh Eslamian, Hamid Zand","doi":"10.3389/fimmu.2025.1570441","DOIUrl":"10.3389/fimmu.2025.1570441","url":null,"abstract":"<p><strong>Background: </strong>Immunosenescence is an important factor in the impaired immune response in older adults and plays a significant role in the development of biological aging. Targeting immunosenescence could present a novel pharmacological approach to mitigating aging and age-related diseases. We aimed to investigate the effect of N-acetylcysteine (NAC) and vitamin D (Vit-D) on the senescence of peripheral blood mononuclear cells (PBMCs).</p><p><strong>Method: </strong>This randomized clinical trial was conducted on older adults with Vit-D deficiency. Eligible participants were randomly assigned to one of four groups to receive either (A) 1000 IU of Vit-D daily (D1) (B), 1000 IU of Vit-D plus 600 mg of NAC daily (D1N) (C), 5000 IU of Vit-D daily (D5), or (D) 5000 IU of Vit-D plus 600 mg of NAC daily (D5N) for 8 weeks. Senescence-associated beta-galactosidase (SA-β-gal) staining, expression of senescence-related genes, and serum inflammatory factors were measured at baseline and after 8 weeks.</p><p><strong>Results: </strong>After the intervention, supplementation with D5N and D5 significantly downregulated <i>p16</i>, interleukin-6 (<i>IL-6</i>), and tumor necrosis factor-α (<i>TNF-α</i>) expression and decreased SA-β-gal activity compared to the D1 group. Additionally, co-administration of NAC with 1000 IU of Vit-D significantly downregulated <i>p16</i> transcripts in PBMCs compared to Vit-D 1000 IU alone. No significant differences were observed between the groups in serum IL-6, C-reactive protein (CRP), or the neutrophil-to-lymphocyte ratio (NLR) after the intervention.</p><p><strong>Conclusions: </strong>The loading dose of Vit-D significantly attenuates senescence in PBMCs of older adults. However, co-administration of NAC with both the standard and loading doses of Vit-D further enhances these beneficial effects.</p><p><strong>Clinical trial registration: </strong>https://irct.behdasht.gov.ir, identifier IRCT20230508058120N1.</p>","PeriodicalId":12622,"journal":{"name":"Frontiers in Immunology","volume":"16 ","pages":"1570441"},"PeriodicalIF":5.7,"publicationDate":"2025-05-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12104082/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144150265","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":"C-reactive protein conformations and their association with the IL-1β/IL-6 pathway in ocular inflammatory conditions.","authors":"Mercedes S Nabaes Jodar, Víctor Llorenç, Marc Figueras-Roca, Maite Sainz de-la-Maza, Alfredo Adán, Blanca Molins","doi":"10.3389/fimmu.2025.1601145","DOIUrl":"10.3389/fimmu.2025.1601145","url":null,"abstract":"<p><strong>Introduction: </strong>C-reactive protein (CRP) plays a critical role in the innate immune system and serves as a biomarker for various inflammatory conditions. CRP is a dynamic protein undergoing conformational changes between pentameric (pCRP) and monomeric (mCRP) conformations. pCRP is the well-established systemic marker of inflammation, while mCRP is associated with localized tissue inflammation.</p><p><strong>Methods: </strong>This study aimed to evaluate systemic levels of pCRP, mCRP, interleukin-6 (IL-6), and interleukin-1β (IL-1β) in patients with a variety of intraocular inflammatory conditions, including diabetic macular edema (DME) and non-infectious uveitis such as Behçet's disease (BD), Birdshot retinochoroidopathy (BSRC), HLA-B27-associated uveitis, and undifferentiated uveitis (UU).</p><p><strong>Results: </strong>A total of 77 subjects were included. mCRP levels were significantly elevated in BD, DME, and UU compared to controls (p = 0.014, p = 0.036, and p = 0.031, respectively). The mCRP/pCRP ratio was also significantly higher in DME and UU (p = 0.035 and p = 0.011, respectively). In addition, a strong positive correlation was observed between IL-6 and IL-1β (ρ = 0.638, p <0.0001). No significant differences in serum levels of pCRP, IL-6, or IL-1β were observed among the groups.</p><p><strong>Conclusions: </strong>These findings suggest that mCRP, rather than pCRP, may be a more specific systemic biomarker for certain intraocular inflammatory conditions. The involvement of the CRP axis and the strong correlation between IL-6 and IL-1β underscore the interaction of these key inflammatory mediators, providing further insight into the targeting of CRP axis for therapeutic purposes.</p>","PeriodicalId":12622,"journal":{"name":"Frontiers in Immunology","volume":"16 ","pages":"1601145"},"PeriodicalIF":5.7,"publicationDate":"2025-05-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12104070/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144150267","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}