Clinical immunology最新文献_第4页

Cerebrospinal fluid exosomal Epstein-Barr virus microRNAs in multiple sclerosis and effects of disease modifying therapies 多发性硬化症脑脊液外泌体爱泼斯坦-巴尔病毒microrna及疾病修饰疗法的效果

IF 3.8 3区医学 Q2 IMMUNOLOGY

Clinical immunology

Pub Date : 2025-10-11 DOI: 10.1016/j.clim.2025.110608

Victoria Hyslop Hvalkof, Malene Bredahl Hansen, Sahla El Mahdaoui, Marie Mathilde Hansen, Jeppe Romme Christensen, Sophie Buhelt, Finn Sellebjerg, Helle Bach Søndergaard

Epstein-Barr virus (EBV) may be crucial for development of multiple sclerosis (MS). EBV encodes 44 microRNAs (miRNAs) that are found in exosomes. We investigated EBV miRNAs in cerebrospinal fluid (CSF) exosomes in 50 newly diagnosed people with relapsing-remitting MS (pwRRMS), 24 with clinically isolated syndromes (CIS), 45 symptomatic controls (SC), 15 anti-CD20 antibody-treated 24 natalizumab (NTZ)-treated pwRRMS. miRNAs were measured by quantitative PCR. Plasma anti-EBNA1 antibody and various CSF biomarkers were measured by immunoassays. ebv-miR-BART13-5p and ebv-miR-BART19-3p were reliably measured. ebv-miR-BART19-3p was lower in pwRRMS and correlated with disease severity. In NTZ-treated pwRRMS, ebv-miR-BART19-3p was higher, correlated with treatment duration, and was associated with soluble B-cell maturation antigen, CD27, and zonula occludens-1. No differences were observed in anti-CD20 antibody-treated pwRRMS. These findings may reflect the presence of more exosome recipient cells in pwRRMS, resulting in fewer exosomes as they become internalized in recipient cells along with their EBV miRNA cargo.

eb病毒（EBV）可能对多发性硬化症（MS）的发展至关重要。EBV编码在外泌体中发现的44种microrna （mirna）。我们研究了50例新诊断的复发-缓解型MS (pwRRMS)， 24例临床分离综合征（CIS）， 45例症状对照（SC）， 15例抗cd20抗体治疗的24例纳他珠单抗（NTZ）治疗的pwRRMS患者脑脊液（CSF）外泌体中的EBV mirna。采用定量PCR检测mirna。采用免疫分析法检测血浆抗ebna1抗体和各种脑脊液生物标志物。Ebv-miR-BART13-5p和ebv-miR-BART19-3p的测定是可靠的。Ebv-miR-BART19-3p在pwRRMS中较低，且与疾病严重程度相关。在ntz治疗的pwRRMS中，ebv-miR-BART19-3p更高，与治疗时间相关，并与可溶性b细胞成熟抗原、CD27和小带闭塞-1相关。抗cd20抗体处理的pwRRMS未见差异。这些发现可能反映了pwRRMS中存在更多的外泌体受体细胞，导致外泌体减少，因为它们与EBV miRNA货物一起被内化在受体细胞中。

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引用次数: 0

Glial-derived neurotrophic factor promotes aberrant basal cell hyperplasia in nasal polyps 神经胶质源性神经营养因子促进鼻息肉异常基底细胞增生。

IF 3.8 3区医学 Q2 IMMUNOLOGY

Clinical immunology

Pub Date : 2025-10-10 DOI: 10.1016/j.clim.2025.110604

Yilin Hou , Lin Sun , Mengqi Su , Weiqiang Yang , Lingchao Ji , Yaqi Zhou , Xiaochan Lu , Na Yin , Jiaqi Zhao , Zihan Qiu , Yi Wei , Weiping Wen , HongYi Hu

Background

Neurotrophins are elevated in nasal polyps (NPs) and/or allergies, exerting neurogenic inflammatory effects. Non-classical glial-derived neurotrophic factor (GDNF) family ligands (GFLs) remain poorly understood in chronic rhinosinusitis with NP (CRSwNP).

Methods

GDNF expression was analyzed in 67 nasal fluids (NFs) and 44 tissues via proteomic, transcriptomic, and immunohistochemical assays. Immunofluorescence co-staining identified GDNF and p63 + basal cells (BCs). Functional studies in human nasal epithelial cells (HNECs) assessed GDNF's affects on proliferation and barrier integrity. Bioinformatics identified regulatory networks and drug candidates.

Results

GDNF existed in NFs and tissues of CRSwNP, with higher abundance in eosinophilic NPs. P63 + BCs expression positively correlates with GDNF levels. GDNF potently activated MAPK/PI3K/Akt signaling in HNECs and induced Ki-67+/p63 + cells proliferation, while reduced distribution of claudin-1 at junctions. miR-204-5p/211-5p and two FDA-approved neuroactive drugs were predicted as GDNF modulators.

Conclusions

GDNF drives aberrant epithelial remodeling in CRSwNP via MAPK/PI3K signaling, highlighting its therapeutic potential for refractory disease.

背景：神经营养因子在鼻息肉（NPs）和/或过敏中升高，发挥神经源性炎症作用。非经典神经胶质源性神经营养因子（GDNF）家族配体（GFLs）在慢性鼻窦炎伴NP （CRSwNP）中的作用尚不清楚。方法：通过蛋白质组学、转录组学和免疫组化分析67种鼻液（NFs）和44种组织中GDNF的表达。免疫荧光共染色鉴定GDNF和p63 + 基底细胞（BCs）。人鼻上皮细胞（HNECs）的功能研究评估了GDNF对增殖和屏障完整性的影响。生物信息学鉴定了监管网络和候选药物。结果：GDNF存在于CRSwNP的NFs和组织中，且在嗜酸性NPs中丰度较高。P63 + BCs表达与GDNF水平呈正相关。GDNF有效激活HNECs中MAPK/PI3K/Akt信号通路，诱导Ki-67+/p63 + 细胞增殖，同时减少连接处cludin -1的分布。预测miR-204-5p/211-5p和两种fda批准的神经活性药物可作为GDNF调节剂。结论：GDNF通过MAPK/PI3K信号驱动CRSwNP异常上皮重塑，突出了其治疗难治性疾病的潜力。

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引用次数: 0

Oral live attenuated polio vaccines induce enhanced T-cell responses with broad antigen recognition compared to inactivated polio vaccines 与灭活脊髓灰质炎疫苗相比，口服脊髓灰质炎减毒活疫苗可诱导具有广泛抗原识别的增强t细胞反应。

IF 3.8 3区医学 Q2 IMMUNOLOGY

Clinical immunology

Pub Date : 2025-10-10 DOI: 10.1016/j.clim.2025.110607

Julia Snyder , Marni Slavik , Patrick Harvey , Roxana Del Rio-Guerra , Bernardo A. Mainou , Alessandro Sette , Beth D. Kirkpatrick , Alba Grifoni , Jessica W. Crothers

Summary

Little is known about the immunologic mechanisms responsible for observed differences in mucosal immunity following vaccination with oral live attenuated polio vaccines (OPVs) compared to inactivated polio vaccines (IPVs). Here, we used a flow cytometric activation-induced marker (AIM)-based approach to investigate vaccine-related differences in T cell response using peripheral blood samples from healthy adults enrolled in two polio vaccine trials. Our findings indicate that vaccination with OPVs (1) enhances CD4+ T cell responses, and (2) expands CD4+ and CD8+ antigen recognition of non-structural proteins. Fecal shedding of OPVs was associated with enhanced T cell responses, and primary CD8+ T cell responses appear to correlate with early control of fecal viral shedding. Our results indicate that OPVs induce broad cellular immunity to polioviruses, which may help explain their enhanced ability to stimulate effective pathogen-specific mucosal immunity.

与灭活脊髓灰质炎疫苗（IPVs）相比，口服脊髓灰质炎减毒活疫苗（OPVs）接种后粘膜免疫差异的免疫学机制尚不清楚。在这里，我们使用基于流式细胞术激活诱导标记（AIM）的方法，使用两项脊髓灰质炎疫苗试验中健康成人的外周血样本，研究疫苗相关的T细胞反应差异。我们的研究结果表明，接种opv(1)增强CD4+ T细胞应答，(2)扩大CD4+和CD8+抗原对非结构蛋白的识别。opv的粪便脱落与增强的T细胞反应有关，而原发性CD8+ T细胞反应似乎与粪便病毒脱落的早期控制有关。我们的研究结果表明，opv诱导对脊髓灰质炎病毒的广泛细胞免疫，这可能有助于解释它们增强刺激有效病原体特异性粘膜免疫的能力。

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引用次数: 0

Altered methylation-related genes expression in B cells of systemic lupus erythematosus patients 系统性红斑狼疮患者B细胞甲基化相关基因表达的改变。

IF 3.8 3区医学 Q2 IMMUNOLOGY

Clinical immunology

Pub Date : 2025-10-08 DOI: 10.1016/j.clim.2025.110606

Amin Azizan , Elham Farhadi , Seyedeh Tahereh Faezi , Majid Alikhani , Mahdi Mahmoudi , Ahmadreza Jamshidi , Mohammad Vodjgani

Background and objective

B cells contribute to systemic lupus erythematosus (SLE) pathogenesis through autoantibody production. DNA hypomethylation in B cells is a hallmark of SLE and may be associated with altered expression of key epigenetic regulators. This study investigated the mRNA expression of DNMT1 and UHRF1, which maintain DNA methylation, and TET2 and TET3, which mediate demethylation, in B cells from SLE patients.

Methods

Participants included individuals with active SLE, inactive SLE, and healthy controls. Purified B cells were stimulated in vitro with anti-human IgM. Gene expression of DNMT1, UHRF1, TET2, and TET3 was quantified by qRT-PCR

Results

At baseline, UHRF1 mRNA expression was significantly decreased, and TET3 expression significantly increased in B cells from active SLE patients compared to controls. Upon anti-IgM activation, further reductions in UHRF1 and increases in TET3 expression were observed in active SLE B cells. DNMT1 and TET2 expression did not differ significantly across groups or conditions.

Conclusion

The altered expression of UHRF1 and TET3 mRNA in B cells from active SLE patients may reflect underlying epigenetic dysregulation associated with disease activity. These findings provide preliminary support for further investigation into their potential involvement in the pathobiology of SLE.

背景与目的：B细胞通过自身抗体的产生参与系统性红斑狼疮（SLE）的发病。B细胞中的DNA低甲基化是SLE的一个标志，可能与关键表观遗传调控因子的表达改变有关。本研究研究了SLE患者B细胞中维持DNA甲基化的DNMT1和UHRF1以及介导去甲基化的TET2和TET3的mRNA表达。方法：参与者包括活动性SLE患者、非活动性SLE患者和健康对照。体外用抗人IgM刺激纯化的B细胞。采用qRT-PCR定量检测DNMT1、UHRF1、TET2和TET3基因表达结果：基线时，与对照组相比，活动性SLE患者B细胞中UHRF1 mRNA表达显著降低，TET3表达显著升高。在抗igm激活后，在活动性SLE B细胞中观察到UHRF1的进一步降低和TET3表达的增加。DNMT1和TET2的表达在不同组或不同条件下无显著差异。结论：活动性SLE患者B细胞中UHRF1和TET3 mRNA表达的改变可能反映了与疾病活动性相关的潜在表观遗传失调。这些发现为进一步研究它们在SLE病理生物学中的潜在作用提供了初步支持。

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引用次数: 0

ILT-2 and ILT-4 expression and donor genotype as factors associated with HSCT outcome il -2和il -4表达和供体基因型与HSCT结果相关。

IF 3.8 3区医学 Q2 IMMUNOLOGY

Clinical immunology

Pub Date : 2025-10-02 DOI: 10.1016/j.clim.2025.110605

Jagoda Siemaszko , Piotr Łacina , Donata Szymczak , Agnieszka Szeremet , Maciej Majcherek , Anna Czyż , Małgorzata Sobczyk-Kruszelnicka , Wojciech Fidyk , Iwona Solarska , Barbara Nasiłowska-Adamska , Patrycja Skowrońska , Maria Bieniaszewska , Agnieszka Tomaszewska , Grzegorz W. Basak , Sebastian Giebel , Tomasz Wróbel , Katarzyna Bogunia-Kubik

Background

NK cell activity after allogeneic haematopoietic stem cell transplantation (HSCT) is still not fully understood. Their cytotoxic activity is modulated by a range of inhibitory and activating surface receptors. Among these, the inhibitory receptors ILT-2 and ILT-4 have yet to be explored in relation to HSCT and its outcomes.

Methods

Genotyping for ILT-2 and ILT-4 was performed using TaqMan assays. ILT-2 and ILT-4 surface expression on NK cells was assessed by flow cytometry. Levels of sHLA-F and sHLA-G were determined using ELISA. mRNA expression of ILT-2, ILT-4 and IFN-γ was measured with quantitative real-time PCR with TaqMan Gene Expression probes.

Results

Presence of donor ILT-2 rs1061681 T allele was associated with increased risk of chronic graft-versus-host disease (cGVHD) (p = 0.0239). Donor ILT-4 rs1128646 T allele was related with decreased risk of overall survival after HSCT (p = 0.0506) and with higher risk of acute GvHD (aGvHD) (p = 0.0834). Serum levels of sHLA-F and sHLA-G were significantly higher at day +30 than day +90 after HSCT (p = 0.0002 and p < 0.0001, respectively). Expression of ILT2 at mRNA level was significantly decreased among recipients with aGvHD (p = 0.0266). ILT-4 expression correlated negatively with expression of interferon gamma (p = 0.0280, R = -0.532). The percentages of LILRB1/ILT-2+ and LILRB2/ILT4+ NK cells were the highest at day +21 after HSCT (p = 0.0014 and p < 0.0001 for ILT-2 and ILT-4, respectively).

Conclusions

Both ILT-2 and ILT-4 inhibitory receptors were found to be associated with allogeneic HSCT outcome. This suggests that ILT receptor expression on NK cells may potentially play a role in post-transplant complications.

背景：同种异体造血干细胞移植（HSCT）后NK细胞的活性尚不完全清楚。它们的细胞毒性活性受一系列抑制和激活表面受体的调节。其中，抑制受体ILT-2和ILT-4与HSCT及其结果的关系尚待探讨。方法：采用TaqMan法对ILT-2和ILT-4进行基因分型。流式细胞术检测NK细胞表面ILT-2和ILT-4的表达。ELISA法检测sHLA-F、sHLA-G水平。采用TaqMan基因表达探针，实时荧光定量PCR检测ILT-2、ILT-4和IFN-γ mRNA表达。结果：供体il -2 rs1061681 T等位基因的存在与慢性移植物抗宿主病（cGVHD）的风险增加相关（p = 0.0239）。供体il -4 rs1128646 T等位基因与HSCT术后总生存风险降低相关（p = 0.0506），与急性GvHD （aGvHD）风险升高相关（p = 0.0834）。血清sHLA-F和sHLA-G水平在HSCT后+30天显著高于+90天（p = 0.0002和p ）结论：发现ILT-2和ILT-4抑制受体与同种异体HSCT预后相关。这表明NK细胞上ILT受体的表达可能在移植后并发症中起潜在的作用。

{"title":"ILT-2 and ILT-4 expression and donor genotype as factors associated with HSCT outcome","authors":"Jagoda Siemaszko , Piotr Łacina , Donata Szymczak , Agnieszka Szeremet , Maciej Majcherek , Anna Czyż , Małgorzata Sobczyk-Kruszelnicka , Wojciech Fidyk , Iwona Solarska , Barbara Nasiłowska-Adamska , Patrycja Skowrońska , Maria Bieniaszewska , Agnieszka Tomaszewska , Grzegorz W. Basak , Sebastian Giebel , Tomasz Wróbel , Katarzyna Bogunia-Kubik","doi":"10.1016/j.clim.2025.110605","DOIUrl":"10.1016/j.clim.2025.110605","url":null,"abstract":"<div><h3>Background</h3><div>NK cell activity after allogeneic haematopoietic stem cell transplantation (HSCT) is still not fully understood. Their cytotoxic activity is modulated by a range of inhibitory and activating surface receptors. Among these, the inhibitory receptors ILT-2 and ILT-4 have yet to be explored in relation to HSCT and its outcomes.</div></div><div><h3>Methods</h3><div>Genotyping for ILT-2 and ILT-4 was performed using TaqMan assays. ILT-2 and ILT-4 surface expression on NK cells was assessed by flow cytometry. Levels of sHLA-F and sHLA-G were determined using ELISA. mRNA expression of <em>ILT-2</em>, <em>ILT-4</em> and <em>IFN-γ</em> was measured with quantitative real-time PCR with TaqMan Gene Expression probes.</div></div><div><h3>Results</h3><div>Presence of donor ILT-2 rs1061681 <em>T</em> allele was associated with increased risk of chronic graft-versus-host disease (cGVHD) (<em>p</em> = 0.0239). Donor ILT-4 rs1128646 <em>T</em> allele was related with decreased risk of overall survival after HSCT (<em>p</em> = 0.0506) and with higher risk of acute GvHD (aGvHD) (<em>p</em> = 0.0834). Serum levels of sHLA-F and sHLA-G were significantly higher at day +30 than day +90 after HSCT (<em>p</em> = 0.0002 and <em>p</em> < 0.0001, respectively). Expression of ILT2 at mRNA level was significantly decreased among recipients with aGvHD (<em>p</em> = 0.0266). ILT-4 expression correlated negatively with expression of interferon gamma (<em>p</em> = 0.0280, R = -0.532). The percentages of <em>LILRB1</em>/ILT-2+ and <em>LILRB2</em>/ILT4+ NK cells were the highest at day +21 after HSCT (<em>p</em> = 0.0014 and <em>p</em> < 0.0001 for ILT-2 and ILT-4, respectively).</div></div><div><h3>Conclusions</h3><div>Both ILT-2 and ILT-4 inhibitory receptors were found to be associated with allogeneic HSCT outcome. This suggests that ILT receptor expression on NK cells may potentially play a role in post-transplant complications.</div></div>","PeriodicalId":10392,"journal":{"name":"Clinical immunology","volume":"281 ","pages":"Article 110605"},"PeriodicalIF":3.8,"publicationDate":"2025-10-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145228466","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}

引用次数: 0

Regarding the “Efgartigimod versus standard of care in new-onset AChR subtype generalized myasthenia gravis: A prospective cohort study” 关于“依夫加替莫德与标准护理相比治疗新发AChR亚型广泛性重症肌无力：一项前瞻性队列研究”。

IF 3.8 3区医学 Q2 IMMUNOLOGY

Clinical immunology

Pub Date : 2025-09-11 DOI: 10.1016/j.clim.2025.110603

Hai-Feng Li , Shi-Min Hu , Wei Han , Yan-Su Guo

引用次数: 0

Clinical, biochemical, and genetic characterization of Lebanese patients with chronic granulomatous disease due to NCF2 pathogenic variants 由NCF2致病变异引起的黎巴嫩慢性肉芽肿病患者的临床、生化和遗传特征

IF 3.8 3区医学 Q2 IMMUNOLOGY

Clinical immunology

Pub Date : 2025-09-05 DOI: 10.1016/j.clim.2025.110596

Youmna El-Orfali , Hagop Mardirossian , Habib Al-Kalamouni , Zeinab El-Zein , Samar Dalle , Dima Khreis , Amani Haddara , Rima Hanna-Wakim , Ghassan Dbaibo , Michel J. Massaad

Chronic Granulomatous Disease (CGD) is caused by mutations in the NADPH oxidase complex that impair the ability of phagocytes to eliminate injested pathogens. As a result, patients with CGD suffer from recurrent infections and chronic inflammation. We report the clinical, biochemical, and genetic basis of the disease in 17 CGD patients from Lebanon. Whole exome sequencing (WES) identified 2 distinct mutations in NCF2 resulting in the deletion of exons 3 and 5, accounting for 82 % of the cases that underwent WES. This high prevalence provided the rationale for a diagnostic strategy involving assessment of NADPH oxidase function, identification of the affected protein, and targeted gene sequencing. Using this approach, 3 additional CGD patients with simmilar deletions were identified, supporting the presence of a founder effect in the Lebanese population. This biochemical and tageted sequencing approach is rapid, reliable, and cost-effective, making it a particularly valuable diagnostic option for families who cannot afford WES.

慢性肉芽肿病（CGD）是由NADPH氧化酶复合物的突变引起的，这种突变损害了吞噬细胞消除注射病原体的能力。因此，CGD患者会出现反复感染和慢性炎症。我们报告了黎巴嫩17例CGD患者的临床、生化和遗传基础。全外显子组测序（WES）在NCF2中发现了2个不同的突变，导致外显子3和5的缺失，占进行WES的病例的82%。这种高患病率为诊断策略提供了基本原理，包括评估NADPH氧化酶功能，鉴定受影响的蛋白质和靶向基因测序。使用这种方法，另外3例具有类似缺失的CGD患者被确定，支持黎巴嫩人群中存在奠基者效应。这种生化和靶向测序方法快速、可靠且具有成本效益，使其成为无法负担WES的家庭特别有价值的诊断选择。

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引用次数: 0

Primary immunodeficiency diseases, inflammation and mitochondrial dysfunction 原发性免疫缺陷疾病，炎症和线粒体功能障碍。

IF 3.8 3区医学 Q2 IMMUNOLOGY

Clinical immunology

Pub Date : 2025-09-02 DOI: 10.1016/j.clim.2025.110595

Salvatore Nesci , Francesca Oppedisano , Giovanni Romeo , Silvia Granata

Primary immunodeficiency diseases (PIDs) are a heterogeneous group of inherited disorders characterized by impaired immune function, leading to increased susceptibility to infections, autoimmunity, and malignancies. While traditionally defined by immune cell defects, emerging evidence highlights the critical role of inflammation in PID pathogenesis. This review explores the intricate relationship between mitochondrial dysfunction and inflammation in PIDs. We examine how genetic defects in PIDs disrupt immune homeostasis, promoting pro-inflammatory states through cytokine dysregulation. Additionally, we discuss the vicious cycle involving oxidative stress, mitochondrial dysfunction, and inflammation, emphasizing the contribution of mitochondrial ROS production, mtDNA damage, and inflammasome activation in sustaining chronic inflammation. Furthermore, we propose that impaired mitochondrial function —potentially through mechanisms involving calcium signalling, ATP synthase regulation, and mitochondrial permeability transition pore formation — may serve as a central link between immune deficiency and hyperinflammation in PIDs. Understanding these complex interactions may provide new insights into the pathogenesis of PIDs and open avenues for targeted therapeutic strategies to improve patient outcomes.

原发性免疫缺陷疾病（pid）是一种异质性的遗传性疾病，其特征是免疫功能受损，导致对感染、自身免疫和恶性肿瘤的易感性增加。虽然传统上由免疫细胞缺陷定义，但新的证据强调了炎症在PID发病机制中的关键作用。本文综述了线粒体功能障碍与炎症之间的复杂关系。我们研究了PIDs中的遗传缺陷如何破坏免疫稳态，通过细胞因子失调促进促炎状态。此外，我们讨论了氧化应激、线粒体功能障碍和炎症的恶性循环，强调了线粒体ROS产生、mtDNA损伤和炎症小体激活在维持慢性炎症中的作用。此外，我们提出线粒体功能受损-可能通过涉及钙信号，ATP合成酶调节和线粒体通透性过渡孔形成的机制-可能是免疫缺陷和PIDs高炎症之间的中心联系。了解这些复杂的相互作用可能为PIDs的发病机制提供新的见解，并为有针对性的治疗策略开辟道路，以改善患者的预后。

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引用次数: 0

B cell receptor repertoires identified by next-generation sequencing showed signatures associated with incomplete immune reconstitution in people living with HIV 新一代测序鉴定的B细胞受体谱显示了与HIV感染者不完全免疫重建相关的特征。

IF 3.8 3区医学 Q2 IMMUNOLOGY

Clinical immunology

Pub Date : 2025-08-31 DOI: 10.1016/j.clim.2025.110594

Yu-Jie Zhan , Wei Liu , Bu-Yi Wang , Bo-Yang Ma , Jia-Ye Wang , Yi-Lin Zhao , Xin-Xin Wang , Yue Jiang , Dan Wang , Li Wang , Hong Ling , Min Zhuang

Incomplete immune reconstitution poses a significant challenge for anti-retroviral therapy (ART) in HIV-infected individuals. The role of B cell receptors (BCRs) in immune reconstitution, a critical aspect of the immune system, has not been well elucidated in ART-experienced people. We analyzed the BCR heavy chain repertoire in immune non-responders (INRs) and immune responders (IRs) by next-generation sequencing. The BCR repertoire of INRs was characterized by a higher proportion of longer HCDR3 and reduced frequencies of IGHV1–69, IGHJ2, and IGHV1–69/IGHJ4 and IGHV5–51/IGHJ4 pairings. INRs, rather than IRs, carried HCDR3 genes which were highly homologous to anti-HIV broadly neutralizing antibodies targeting the six-helix bundle (6HB) in envelope gp41. The plasmas of INRs also exhibited an increased reactivity to FPPR-N36, a peptide within 6HB. These findings indicated a potential association between BCR, antibodies to partial gp41, and incomplete immune reconstitution and provided new perspectives for understanding the BCR repertoire and immune reconstitution.

不完全的免疫重建对艾滋病毒感染者的抗逆转录病毒治疗（ART）提出了重大挑战。B细胞受体（BCRs）在免疫重建中的作用是免疫系统的一个关键方面，但在经历过art治疗的人群中尚未得到很好的阐明。我们利用新一代测序技术分析了免疫无应答者（INRs）和免疫应答者（IRs）的BCR重链库。INRs的BCR库的特点是HCDR3较长比例较高，IGHV1-69、IGHJ2、IGHV1-69/IGHJ4和IGHV5-51/IGHJ4配对频率较低。INRs而不是IRs携带HCDR3基因，这些基因与靶向包膜gp41中六螺旋束（6HB）的抗hiv广泛中和抗体高度同源。INRs的血浆也表现出对fpr - n36 （6HB内的肽）的反应性增加。这些发现提示了BCR、部分gp41抗体和不完全免疫重建之间的潜在关联，并为理解BCR库和免疫重建提供了新的视角。

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引用次数: 0

Staphylococcus aureus induces miR-21 expression to promote bacterial persistence during nasal colonisation 金黄色葡萄球菌诱导miR-21表达，促进细菌在鼻腔定植过程中的持久性。

IF 3.8 3区医学 Q2 IMMUNOLOGY

Clinical immunology

Pub Date : 2025-08-29 DOI: 10.1016/j.clim.2025.110593

Alanna M. Kelly , Emilio G. Vozza , Brenda Morris , Seán C. Cahill , Charlotte M. Leane , Sinéad C. Corr , Rachel M. McLoughlin

Staphylococcus aureus nasal colonisation is commonplace among healthy individuals, yet the immune mechanisms enabling bacterial persistence remain unclear. S. aureus drives local immunosuppression during nasal colonisation to facilitate persistence. This study reveals that S. aureus subverts microRNA-21 activity to promote IL-10 production within nasal tissue, while simultaneously impeding local pro-inflammatory responses. MiR-21 activity helps establish a S. aureus-induced immunosuppressive microenvironment, which supports S. aureus persistence. Macrophages, which are key IL-10 producers, rapidly upregulate miR-21 upon S. aureus exposure. MiR-21 expression also coincides with an increase in intracellular survival of S. aureus within macrophages. Furthermore, S. aureus represses macrophage glycolysis to promote intracellular survival, which is dependent upon miR-21. Upon S. aureus colonisation, miR-21^−/− mice demonstrate an overall improved bacterial clearance compared to their wild-type counterparts. These findings highlight the targeting of miR-21, which controls glycolytic activity in macrophages, as a potential avenue to reducing bacterial persistence during S. aureus colonisation.

金黄色葡萄球菌鼻腔定植在健康个体中很常见，但使细菌持续存在的免疫机制尚不清楚。金黄色葡萄球菌在鼻腔定植过程中驱动局部免疫抑制以促进持久性。本研究表明，金黄色葡萄球菌破坏microRNA-21活性，促进鼻腔组织内IL-10的产生，同时阻碍局部促炎反应。MiR-21活性有助于建立金黄色葡萄球菌诱导的免疫抑制微环境，支持金黄色葡萄球菌的持久性。巨噬细胞是关键的IL-10产生者，在金黄色葡萄球菌暴露后迅速上调miR-21。MiR-21的表达也与巨噬细胞内金黄色葡萄球菌细胞内存活率的增加相吻合。此外，金黄色葡萄球菌抑制巨噬细胞糖酵解以促进细胞内存活，这依赖于miR-21。在金黄色葡萄球菌定植后，miR-21-/-小鼠与WT对应物相比，表现出总体上改善的细菌清除率。这些发现将miR-21作为靶点，它控制巨噬细胞中的糖酵解活性，作为减少金黄色葡萄球菌定殖期间细菌持久性的潜在途径。

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引用次数: 0