Immunobiology最新文献_第3页

Higher levels of urinary extracellular vesicles and immune mediators are related to acute infection severity during the post-COVID period 尿细胞外囊泡和免疫介质水平升高与新冠肺炎后急性感染严重程度有关

IF 2.3 4区医学 Q3 IMMUNOLOGY

Immunobiology

Pub Date : 2025-11-01 DOI: 10.1016/j.imbio.2025.153142

Evelyn Maciel de Oliveira , Camila Carvalho , Natalia Fonseca do Rosário , Carla Rodrigues , Iris Braga da Silva , Alice Ramos , Fabiana Rabe Carvalho , Pedro Barbosa , Fernanda G. De Felice , Mauro Jorge Cabral-Castro , Jocemir Ronaldo Lugon , Thalia Medeiros , Andrea Alice Silva

Introduction: We investigated circulating and urinary inflammatory mediators and extracellular vesicles (EVs) in association with clinical and laboratory findings during the post-COVID-19 (coronavirus disease 2019) period. Methods: A cross-sectional study was conducted with individuals with history of COVID-19 stratified according to the presence of post-COVID condition (PCC) and hospitalization during the acute phase. Circulating and urinary levels of 27 inflammatory mediators were quantified by multiplex assays. EVs were isolated by differential centrifugation and assessed by nanoscale flow cytometry, nanoparticle tracking analysis, and transmission electron microscopy. Results: We included 78 participants (55 ± 14.6 years-old, 79.5 % females), of whom 56 (71.8 %) had PCC. Of these, 18 (32 %) required hospitalization during COVID-19. No differences between groups were observed regarding plasma EVs, but hospitalized PCC patients presented lower levels of circulant interleukin (IL)-9 (p = 0.03), higher monocyte-to-lymphocyte ratio (p = 0.03), prothrombin time (p = 0.02), and lactate dehydrogenase (p = 0.01). In addition, higher levels of total urinary EVs (uEVs, p = 0.006) and uIL-4 (p = 0.01), chemokine (CC motif) ligand (CCL)-2 (p = 0.02), CCL-11 (p = 0.002), and granulocyte-macrophage colony-stimulating factor (p = 0.04) were observed in the same group. Likewise, individuals infected before vaccination presented higher total uEVs (p = 0.003) and urinary CCL-11 (p = 0.01), and multiple episodes of COVID-19 were associated with higher urinary interferon-γ (p = 0.04) and IL-1Ra (p = 0.03). Conclusion: Our results may suggest a possible remnant renal inflammatory process in PCC patients who had moderate-to-severe acute COVID-19.

前言：我们研究了循环和尿路炎症介质和细胞外囊泡（ev）与covid -19（2019冠状病毒病）后时期临床和实验室结果的相关性。方法：采用横断面研究方法，对有COVID-19病史的个体进行分层，按是否存在COVID-19后症状（PCC）和急性期住院情况进行分层。通过多重测定法定量27种炎症介质的循环和尿液水平。通过差速离心分离ev，并通过纳米级流式细胞术、纳米颗粒跟踪分析和透射电镜进行评估。结果：我们纳入78名参与者（55±14.6岁，79.5%为女性），其中56名（71.8%）患有PCC。其中18人（32%）在COVID-19期间需要住院治疗。各组间血浆EVs无差异，但住院PCC患者循环白细胞介素(IL)-9水平较低（p = 0.03），单核细胞与淋巴细胞比值较高（p = 0.03），凝血酶原时间（p = 0.02），乳酸脱氢酶（p = 0.01）。此外，尿总ev （uEVs, p = 0.006）和il -4 （p = 0.01）、趋化因子（CC motif）配体(CCL)-2 （p = 0.02）、CCL-11 （p = 0.002）和粒细胞-巨噬细胞集落刺激因子（p = 0.04）水平均高于对照组。同样，接种疫苗前感染的个体总uEVs （p = 0.003）和尿CCL-11 （p = 0.01）较高，多次发作的COVID-19与尿干扰素-γ (p = 0.04)和IL-1Ra （p = 0.03）较高相关。结论：我们的研究结果可能提示中重度急性COVID-19的PCC患者可能存在残留的肾脏炎症过程。

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引用次数: 0

Corrigendum to “UMI-77 targets MCL-1 to activate mitophagy and ameliorate periodontitis in mice” [Immunobiology 230(5) (2025) 153108] “uni -77靶向MCL-1激活线粒体自噬并改善小鼠牙周炎”的更正[免疫生物学230(5)(2025)153108]。

IF 2.3 4区医学 Q3 IMMUNOLOGY

Immunobiology

Pub Date : 2025-11-01 DOI: 10.1016/j.imbio.2025.153120

Dalei Sun , Shu Ouyang , Xiaoxuan Xu , Jingjing Yan , Heqian Wang , Chenkai Lan , Wubin Ouyang , Liangjun Zhong , Jun Lin

引用次数: 0

Absence of complement terminal pathway activity in C6-deficient mice prolongs survival in a mouse model of severe malarial infection 在严重疟疾感染小鼠模型中，缺乏补体末端通路活性的c6缺陷小鼠延长了生存期。

IF 2.3 4区医学 Q3 IMMUNOLOGY

Immunobiology

Pub Date : 2025-11-01 DOI: 10.1016/j.imbio.2025.153140

Tomoaki Kamiya , Yuki Miyasaka , Hangsoo Kim , Sosuke Fukui , Masatoshi Inoue , Masatoshi Ishigami , Yasuhiro Suzuki , Shoichi Maruyama , Tamio Ohno , Timothy R. Hughes , B. Paul Morgan , Masashi Mizuno

Background

Malaria is an important and serious parasite-induced disease associated with severe anemia and multiple organ failure (MOF) that can be lethal in humans. We explored the contribution of the terminal pathway of complement in a mouse model of malaria-induced lethal MOF following infection with Plasmodium (P.) bergei.

Methods

We compared organ damage and survival between C57BL/6 J mice deficient in the terminal pathway component C6 (C6def) and wild type C57BL/6 J mice (WT) after intraperitoneal injection of 10⁶ P. bergei-parasitized erythrocytes. We measured survival, relevant blood parameters, assessed severity of injury and complement activation in relevant organs.

Results

All WT mice died between 7 and 13 days after exposure to the parasite challenge; in contrast, C6def mice showed prolonged survival with 80 % alive at day 20, although all then died by day 26. Parasite load and anemia at day 7 were similar in C6def and WT mice. Liver and lung injuries, fibrosis and organ complement deposition assessed at day 7 post-infection were significantly milder in C6def mice compared to WT. Blood platelet count at day 7 post-infection was markedly reduced in WT but not in C6def mice; in contrast, white cell count was increased and hemoglobin levels decreased to similar degrees in WT and C6def mice post-infection. Albumin levels were reduced, significantly more in WT, while blood markers of liver injury were increased, significantly more in WT. Serum levels of complement activation product, C5a, and IL6 were increased in both groups, the latter significantly higher in WT versus C6def mice.

Conclusion

We show that complement terminal pathway activation exacerbates organ injuries and thrombocytopenia associated with P. bergei infection, contributing to rapid progression to death in the model. Inhibition of terminal pathway activation in human malarial infections using available drugs might slow progression to organ failure, extending the window of opportunity for the effective use of anti-malarial medicines.

背景：疟疾是一种重要且严重的寄生虫引起的疾病，与人类严重贫血和多器官衰竭（MOF）相关，可致人死亡。我们探索了补体终末通路在感染柏氏疟原虫后疟疾诱导的致死性MOF小鼠模型中的作用。方法：腹腔注射106P后，比较末端通路组分C6 （C6def）缺失的C57BL/6 J小鼠和野生型C57BL/6 J小鼠（WT）的器官损伤和存活情况。bergei-parasitized红细胞。我们测量了存活率，相关血液参数，评估了损伤的严重程度和相关器官的补体激活。结果：所有WT小鼠在暴露于寄生虫攻击后7 ~ 13天死亡；相比之下，C6def小鼠的存活时间较长，在第20天有80%的小鼠存活，但在第26天全部死亡。C6def和WT小鼠第7天的寄生虫载量和贫血相似。感染后第7天，C6def小鼠的肝和肺损伤、纤维化和器官补体沉积明显轻于WT。感染后第7天，WT小鼠的血小板计数明显减少，而C6def小鼠则没有；相比之下，WT和C6def小鼠感染后白细胞计数增加，血红蛋白水平下降程度相似。白蛋白水平降低，WT组明显更多，而肝损伤血液标志物升高，WT组明显更多。两组血清补体活化产物、C5a和il - 6水平升高，后者在WT组明显高于C6def小鼠。结论：我们的研究表明，补体末端通路激活加剧了与伯格氏杆菌感染相关的器官损伤和血小板减少症，在模型中促进了快速进展至死亡。使用现有药物抑制人类疟疾感染的终末通路激活可能会减缓器官衰竭的进展，从而扩大有效使用抗疟疾药物的机会之窗。

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引用次数: 0

Anti-retroviral treatment of HIV infected individuals improves the ex vivo generation of memory-like NK cells HIV感染者的抗逆转录病毒治疗改善了记忆样NK细胞的体外生成。

IF 2.3 4区医学 Q3 IMMUNOLOGY

Immunobiology

Pub Date : 2025-11-01 DOI: 10.1016/j.imbio.2025.153127

Kalavati Lalsare MSc, Shubhangi Bichare MSc, Sheetal Mulay MSc, Rajani D. Bagul MSW, Suvarna Sane M.Phil, Madhuri Thakar PhD

The ability of Natural Killer (NK) cells, to generate memory-like responses against viruses including – HIV, opened up possibility of their application as immune therapy. We attempted to generate memory-like NK cells from HIV exposed and unexposed primary NK cells. The PBMCs of HIV uninfected and infected individuals (LTNPs, ART experienced and with progressive disease) were preactivated with cytokine cocktail (CC) of IL12, IL 15 and IL 18 with or without HIV-1 Env C or only IL 15 and restimulated with CC + HIV-1 Env C after seven days' rest. The CD56+ NK cells from the cultures were assessed for IFN-γ, TNF-α, and perforin secretion and expression of CD107a using multiparametric flow cytometry. Higher functionality was observed in case of pre-activation with CC with or without HIV-1 Env C as compared to only Il 15 across study groups. However, the functionality of the generated memory -like NK cells was significantly higher in case of LTNPs and the ART experienced individuals only. Low frequency of functional NK cells generated from HIV unexposed NK cells indicate probable specificity to HIV. The memory-like NK cells from ART experienced individuals generated after CC and CC+ HIV-1C preactivation showed good proliferating ability and also an ability to lyse the allogenic HIV infected CD4+ T cells. This work highlighted that HIV specific memory-like NK cells can be generated from the NK cells of HIV infected individuals with robust immune status after pre-activation with cytokine cocktail with or without HIV-1C. Although preliminary, these findings suggest that memory-like NK cells could have potential for use in immunotherapy aimed at clearing viral reservoirs.

自然杀伤（NK）细胞能够产生类似记忆的反应来对抗包括HIV在内的病毒，这为它们作为免疫疗法的应用开辟了可能性。我们试图从HIV暴露和未暴露的原代NK细胞中产生记忆样NK细胞。用IL - 12、IL - 15和IL - 18的细胞因子混合物（CC）预先激活未感染HIV和感染HIV的个体（ltnp、ART经历者和疾病进展者），伴或不伴HIV-1 Env C或仅伴IL - 15，并在休息7天后用CC + HIV-1 Env C重新激活PBMCs。采用多参数流式细胞术检测培养的CD56+ NK细胞的IFN-γ、TNF-α、穿孔素分泌和CD107a的表达。与仅Il - 15相比，在具有或不具有HIV-1 Env C的CC预激活情况下，观察到更高的功能。然而，仅在ltnp和ART经历个体的情况下，生成的记忆样NK细胞的功能显着更高。从HIV未暴露的NK细胞中产生的功能性NK细胞的低频率表明可能对HIV具有特异性。在CC和CC+ HIV- 1c预激活后，来自ART经历个体的记忆样NK细胞表现出良好的增殖能力，并且能够溶解同种异体HIV感染的CD4+ T细胞。这项工作强调，HIV特异性记忆样NK细胞可以由具有强大免疫状态的HIV感染个体的NK细胞通过细胞因子鸡尾酒预激活产生，无论是否具有HIV- 1c。虽然是初步的，但这些发现表明，记忆样NK细胞可能有潜力用于旨在清除病毒库的免疫治疗。

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引用次数: 0

The anti-tumor and immunomodulatory effect of α-tocopherol on tumor microenvironment in an in vitro model of colon cancer α-生育酚对结肠癌体外模型肿瘤微环境的抗肿瘤和免疫调节作用。

IF 2.3 4区医学 Q3 IMMUNOLOGY

Immunobiology

Pub Date : 2025-11-01 DOI: 10.1016/j.imbio.2025.153138

Tahereh Azari , Fatemeh Sadeghi , Kosar Malekpour , Farzad Nasri , Elahe Safari

Background

Colorectal cancer (CRC) requires effective preventive measures due to its high prevalence, mortality rate, and impact on patients' lives. Therefore, this study aimed to assess the immunomodulatory effects of α-tocopherol (α-TOC) within the tumor microenvironment (TME) of CRC using a co-culture model.

Methods

To characterize the biological effects of vitamin E, apoptosis assays, scratch tests, and real-time PCR were performed to investigate the direct effect of α-TOC (2.2, 22, and 220 μM) on the viability, migration, and pathway mechanisms of the SW480 CRC cell line. PBMCs (peripheral blood mononuclear cells) were co-cultured with the SW480 to assess the effects within the TME and then treated with α-TOC. We evaluated the effect of α-TOC on the viability of PBMC and the co-culture of PBMC+SW480 using an MTT assay. Additionally, we performed ELISA and flow cytometry to assess the effect of α-TOC on the secretion of IFN-γ and the population of immunomodulatory cells such as MDSCs and Treg cells, respectively.

Results

Our findings revealed that α-TOC significantly induced apoptosis in SW480 cells and promoted the proliferation of PBMCs (P < 0.05). In the co-culture group (PBMC+SW480), α-TOC stimulated PBMC proliferation, increased IFN-γ secretion, and reduced the population of MDSCs (P < 0.05). However, α-TOC did not significantly affect the Treg population.

Conclusion

These results suggest that, in addition to its direct anti-tumor effects, α-TOC also shows immunomodulatory properties in the context of colon cancer in an in vitro model.

背景：结直肠癌（Colorectal cancer， CRC）发病率高、死亡率高、影响患者生活，需要有效的预防措施。因此，本研究旨在通过共培养模型评估α-生育酚（α-TOC）在结直肠癌肿瘤微环境（TME）中的免疫调节作用。方法：采用细胞凋亡实验、划痕实验和实时荧光定量PCR等方法，研究α-TOC （2.2 μM、22 μM和220 μM）对SW480 CRC细胞株的活性、迁移和通路机制的直接影响。外周血单个核细胞（pbmc）与SW480共培养，观察其在TME内的作用，然后用α-TOC处理。我们用MTT法评估α-TOC对PBMC和PBMC+SW480共培养活力的影响。此外，我们通过ELISA和流式细胞术分别评估α-TOC对IFN-γ分泌和免疫调节细胞（如MDSCs和Treg细胞）数量的影响。结果：α-TOC可显著诱导SW480细胞凋亡，促进PBMCs增殖(P)。结论：α-TOC除具有直接的抗肿瘤作用外，在体外结肠癌模型中还具有免疫调节作用。

{"title":"The anti-tumor and immunomodulatory effect of α-tocopherol on tumor microenvironment in an in vitro model of colon cancer","authors":"Tahereh Azari , Fatemeh Sadeghi , Kosar Malekpour , Farzad Nasri , Elahe Safari","doi":"10.1016/j.imbio.2025.153138","DOIUrl":"10.1016/j.imbio.2025.153138","url":null,"abstract":"<div><h3>Background</h3><div>Colorectal cancer (CRC) requires effective preventive measures due to its high prevalence, mortality rate, and impact on patients' lives. Therefore, this study aimed to assess the immunomodulatory effects of α-tocopherol (α-TOC) within the tumor microenvironment (TME) of CRC using a co-culture model.</div></div><div><h3>Methods</h3><div>To characterize the biological effects of vitamin E, apoptosis assays, scratch tests, and real-time PCR were performed to investigate the direct effect of α-TOC (2.2, 22, and 220 μM) on the viability, migration, and pathway mechanisms of the SW480 CRC cell line. PBMCs (peripheral blood mononuclear cells) were co-cultured with the SW480 to assess the effects within the TME and then treated with α-TOC. We evaluated the effect of α-TOC on the viability of PBMC and the co-culture of PBMC+SW480 using an MTT assay. Additionally, we performed ELISA and flow cytometry to assess the effect of α-TOC on the secretion of IFN-γ and the population of immunomodulatory cells such as MDSCs and Treg cells, respectively.</div></div><div><h3>Results</h3><div>Our findings revealed that α-TOC significantly induced apoptosis in SW480 cells and promoted the proliferation of PBMCs (<em>P</em> < 0.05). In the co-culture group (PBMC+SW480), α-TOC stimulated PBMC proliferation, increased IFN-γ secretion, and reduced the population of MDSCs (<em>P</em> < 0.05). However, α-TOC did not significantly affect the Treg population<strong>.</strong></div></div><div><h3>Conclusion</h3><div>These results suggest that, in addition to its direct anti-tumor effects, α-TOC also shows immunomodulatory properties in the context of colon cancer in an <em>in vitro</em> model.</div></div>","PeriodicalId":13270,"journal":{"name":"Immunobiology","volume":"230 6","pages":"Article 153138"},"PeriodicalIF":2.3,"publicationDate":"2025-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145512641","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}

引用次数: 0

The Role of WNT5A-mediated proteomic and phosphoproteomic regulatory networks in rheumatoid arthritis wnt5a介导的蛋白质组学和磷酸化蛋白质组学调节网络在类风湿关节炎中的作用

IF 2.3 4区医学 Q3 IMMUNOLOGY

Immunobiology

Pub Date : 2025-11-01 DOI: 10.1016/j.imbio.2025.153137

Ping Jiang , Daxi Ma , Youji Jia , Honghong Ma , Yajuan Guo , Juhua Zhang , Wei Yan , Xiaobing Xi

Objective

This study aims to investigate the role of the WNT5A signaling pathway in rheumatoid arthritis (RA) fibroblast-like synoviocytes (FLS) and uncover the impact of WNT5A on cellular function and signal transduction through proteomic and phosphoproteomic analyses.

Methods

MH7A cells were treated with recombinant WNT5A (rhWNT5A), and differential expression proteins (DEPs) and phosphoproteins (DEPPs) were identified through proteomic and phosphoproteomic analyses. Data were further analyzed via volcano plots, heatmaps, enrichment analysis, and protein-protein interaction (PPI) networks to identify key biological processes and signaling pathways regulated by WNT5A.

Results

Significant changes in the expression of numerous DEPs and DEPPs were observed following rhWNT5A treatment, including proteins closely related to lipid metabolism, cell migration, inflammation, and cell proliferation. PPI network analysis revealed that key regulatory proteins, such as HNRNPA1, RANBP2, BCLAF1, NPM1, and SMARCA4, occupy central positions in the network. Enrichment analysis indicated that WNT5A influences essential signaling pathways, such as AMPK, mTOR, VEGFA-VEGFR2, Notch, and endoplasmic reticulum stress, regulating cellular energy metabolism, inflammatory response, and cytoskeletal remodeling. Kinase activity analysis identified significant changes in kinases such as CDK1, CSNK2A1, EEF2K, AURKA, and AURKB, which were further integrated into the kinase-substrate regulatory network.

Conclusion

This study demonstrates that WNT5A significantly influences the biological functions and inflammatory responses of RA-FLS by regulating key biological processes and signaling pathways. The integrated proteomic and phosphoproteomic analyses provide insights into the potential mechanisms and regulatory networks of WNT5A in RA, suggesting its application as a potential therapeutic target.

目的研究WNT5A信号通路在类风湿关节炎（RA）成纤维细胞样滑膜细胞（FLS）中的作用，并通过蛋白质组学和磷酸化蛋白质组学分析揭示WNT5A对细胞功能和信号转导的影响。方法用重组WNT5A （rhWNT5A）处理smh7a细胞，通过蛋白质组学和磷酸化蛋白质组学分析鉴定差异表达蛋白（DEPs）和磷酸化蛋白（DEPPs）。通过火山图、热图、富集分析和蛋白相互作用（PPI）网络进一步分析数据，以确定WNT5A调控的关键生物学过程和信号通路。结果rhWNT5A处理后，多种DEPs和DEPPs的表达发生了显著变化，包括与脂质代谢、细胞迁移、炎症和细胞增殖密切相关的蛋白。PPI网络分析显示，HNRNPA1、RANBP2、BCLAF1、NPM1和SMARCA4等关键调控蛋白在网络中占据中心位置。富集分析表明，WNT5A影响AMPK、mTOR、VEGFA-VEGFR2、Notch、内质网应激等重要信号通路，调节细胞能量代谢、炎症反应和细胞骨架重塑。激酶活性分析发现CDK1、CSNK2A1、EEF2K、AURKA和AURKB等激酶发生了显著变化，这些激酶进一步整合到激酶-底物调控网络中。结论本研究表明WNT5A通过调控RA-FLS的关键生物学过程和信号通路，显著影响RA-FLS的生物学功能和炎症反应。综合蛋白质组学和磷酸化蛋白质组学分析提供了WNT5A在RA中的潜在机制和调控网络的见解，提示其作为潜在的治疗靶点的应用。

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引用次数: 0

Copper regulates the expression of immune genes in microglial cells in vitro 铜在体外调节小胶质细胞免疫基因的表达

IF 2.3 4区医学 Q3 IMMUNOLOGY

Immunobiology

Pub Date : 2025-11-01 DOI: 10.1016/j.imbio.2025.153145

Laura Craciun, Sandra E. Muroy, Kaoru Saijo

Copper, a transition metal, plays crucial roles in various physiological functions, including those of the nervous and immune systems. Dysregulation of copper homeostasis is linked to several diseases, such as neurodegenerative diseases. Since dysfunctional microglial immunity can also contribute to such diseases, we investigated the role of copper in microglial immunity. Currently, the roles of copper in microglial immunity are considered complex and multifaceted, with both anti- and pro-inflammatory effects having been proposed. In the current study, we found that both increased and decreased copper levels suppressed lipopolysaccharide (LPS)-mediated inflammation in microglial cells, as determined by RT-qPCR analysis. RNA sequencing (RNA-seq) analysis confirmed that increased copper levels reduced the inflammatory response to LPS; however, it also showed that decreased copper levels affected genes involved in cell proliferation, transcription, and autophagosome regulation. These findings suggest that copper is vital for maintaining normal immune functions in microglia, and that both copper excess and deficiency can disrupt microglial immunity.

铜是一种过渡金属，在包括神经和免疫系统在内的各种生理功能中起着至关重要的作用。铜稳态失调与多种疾病有关，如神经退行性疾病。由于功能失调的小胶质细胞免疫也可能导致这些疾病，我们研究了铜在小胶质细胞免疫中的作用。目前，铜在小胶质细胞免疫中的作用被认为是复杂和多方面的，已经提出了抗炎和促炎作用。在目前的研究中，我们发现，通过RT-qPCR分析，铜水平的升高和降低都抑制了小胶质细胞中脂多糖（LPS）介导的炎症。RNA测序（RNA-seq）分析证实，铜水平升高可降低对LPS的炎症反应；然而，研究也表明，铜水平的降低会影响参与细胞增殖、转录和自噬体调节的基因。这些发现表明，铜对于维持小胶质细胞的正常免疫功能至关重要，铜的过量和缺乏都会破坏小胶质细胞的免疫功能。

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引用次数: 0

The impact of neutralizing anti-IFN-γ autoantibodies on GBP5 expression and monocyte dysfunction in adult-onset immunodeficiency 中和抗ifn -γ自身抗体对成人发病免疫缺陷中GBP5表达和单核细胞功能障碍的影响。

IF 2.3 4区医学 Q3 IMMUNOLOGY

Immunobiology

Pub Date : 2025-11-01 DOI: 10.1016/j.imbio.2025.153134

Kanokporn Sornsuwan , On-anong Juntit , Kanyarat Thongheang , Ekkarat Wongsawat , Chatchai Tayapiwatana , Umpa Yasamut

Anti-interferon gamma (IFN-γ) autoantibodies (AIGAs) are linked to opportunistic infections in adult-onset immunodeficiency (AOID). These autoantibodies, particularly those recognizing the C-terminal linear epitope (P128–143) and B27 epitope, block IFN-γ functions in monocytes, contributing to disease. In a retrospective analysis of residual plasma from 45 AOID patients, we confirmed the presence of AIGAs by indirect ELISA and evaluated their capacity to neutralize IFN-γ–induced MHC-II expression. All samples showed neutralizing capability, with varying epitope recognition: 10 samples had AIGAs which recognize both epitopes, 7 had B27 epitope-recognizing AIGAs, 12 had P128–143 epitope-recognizing AIGAs, and 16 had neither. Inhibition levels ranged from 36.5 % to 91.6 %. Five representative samples containing at least B27 epitope-recognizing AIGAs could inhibit guanylate binding protein 5 (GBP5) expression, crucial for pathogen killing. Additionally, high levels of neutralizing AIGAs persisted in patients with active and stable diseases. Overall, the data underscore the relationship between neutralizing AIGA levels, population characteristics, and persistence of AIGAs with monocyte dysfunction and disease outcome.

抗干扰素γ (IFN-γ)自身抗体（aiga）与成人发病免疫缺陷（AOID）的机会性感染有关。这些自身抗体，特别是识别c端线性表位（P128-143）和B27表位的自身抗体，会阻断单核细胞中IFN-γ的功能，从而导致疾病。在对45例患者的残留血浆的回顾性分析中，我们通过间接ELISA证实了aiga的存在，并评估了它们中和IFN-γ诱导的MHC-II表达的能力。所有样品均表现出中和能力，但具有不同的表位识别能力：10个样品具有同时识别两种表位的aiga， 7个样品具有识别B27表位的aiga， 12个样品具有识别P128-143表位的aiga， 16个样品两者均不具有。抑制水平从36.5%到91.6%不等。含有至少B27表位识别AIGAs的5个代表性样品可以抑制鸟苷酸结合蛋白5 （guanyate binding protein 5, GBP5）的表达，这是杀死病原体的关键。此外，在活动性和稳定性疾病患者中，高水平的中和性AIGAs持续存在。总的来说，这些数据强调了中和AIGA水平、群体特征和AIGA持续存在与单核细胞功能障碍和疾病结局之间的关系。

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引用次数: 0

The grand escape – how pathogens outsmart the human complement system 大逃亡——病原体如何智胜人体补体系统。

IF 2.3 4区医学 Q3 IMMUNOLOGY

Immunobiology

Pub Date : 2025-11-01 DOI: 10.1016/j.imbio.2025.153126

A.A. Nowacka , L. Sordo Vieira , V. Petr , B. Fageräng , R. Würzner , M. Ohms

Infectious diseases remain a significant cause of mortality and morbidity worldwide. Complement is a critical component in the defense against pathogens and despite their great differences, viruses, bacteria, fungi, and protists have all developed similar mechanisms of evasion from the human complement system. Using examples from four microbial groups (viruses, bacteria, fungi and protists), this review expands on examples of these different mechanisms of evasion. The mechanisms are grouped as (A) avoidance of recognition, (B) avoidance of eradication, (C) avoidance of activation and function, or (D) use of the complement proteins for entry into the host, in accordance with the classification initially proposed in 1999. Furthermore, this review will expand on novel descriptions of complement evasion, for example involving intracellular complement. Taken toge complement evasion is an essential tool used by pathogens not only in a defensive manner, protecting the pathogen from the host, but can also employed in an aggressive manner to aid the invasion of the host. Understanding these mechanisms has already influenced diagnostic and therapeutic tools, including vaccine development, and a further expansion of evasion molecules as biomarkers, vaccines or targets for therapy appears likely in the future.

传染病仍然是全世界死亡和发病的一个重要原因。补体是防御病原体的关键组成部分，尽管它们之间存在很大差异，但病毒、细菌、真菌和原生生物都发展出类似的逃避人体补体系统的机制。本文以四种微生物类群（病毒、细菌、真菌和原生生物）为例，详细介绍了这些不同的逃避机制。根据1999年最初提出的分类，这些机制被分为(A)避免识别，(B)避免根除，(C)避免激活和功能，或(D)利用补体蛋白进入宿主。此外，本综述将扩展对补体逃避的新描述，例如涉及细胞内补体。总的来说，补体逃避是病原体使用的重要工具，不仅以防御的方式保护病原体免受宿主的侵害，而且还可以以积极的方式帮助入侵宿主。了解这些机制已经影响了包括疫苗开发在内的诊断和治疗工具，并且在未来可能会进一步扩大逃避分子作为生物标志物、疫苗或治疗靶点的范围。

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引用次数: 0

Dual-phase study of CD4+CXCR4+ T cells in Mycoplasma pneumoniae pneumonia: clinical correlations in children and therapeutic exploration with tofacitinib in mice CD4+CXCR4+ T细胞在肺炎支原体肺炎中的双期研究：儿童的临床相关性及托法替尼在小鼠中的治疗探索

IF 2.3 4区医学 Q3 IMMUNOLOGY

Immunobiology

Pub Date : 2025-11-01 DOI: 10.1016/j.imbio.2025.153136

Kaiwen Wang , Li Guo , Yongqi Zhang , Haiting Yang , Zhenghan Zhao , Hui Du , Jiangfeng Zhao

<div><h3>Objective</h3><div>This study had two primary objectives. First, we aimed to investigate whether differential expression of the chemokine receptor CXCR4 on CD4<sup>+</sup> T lymphocytes could serve as a distinguishing immunological feature between pediatric patients with severe <em>Mycoplasma pneumoniae</em> pneumonia (SMPP) and those with on- Non-severe MPP. Second, we sought to explore the therapeutic potential of the JAK inhibitor Tofacitinib in MPP by examining its effects on CXCR4 pathway modulation, using both clinical observations and experimental validation through an established animal model of MPP.</div></div><div><h3>Methods</h3><div>We conducted a prospective cohort study involving 267 pediatric patients diagnosed with MPP at Jiading District Central Hospital between 2023 and 2024, comprising 42 SMPP cases and 225 Non-severe MPP cases. Baseline clinical and laboratory parameters were systematically collected within 24 h of hospital admission. Flow cytometry was employed to quantify the percentage of CD4<sup>+</sup> T cells expressing CXCR4 (CD4<sup>+</sup>CXCR4<sup>+</sup>) in peripheral blood samples by flow cytometry. For mechanistic investigation, we established a murine model of MPP to evaluate the immunomodulatory effects of Tofacitinib. Treatment groups received either vehicle control or Tofacitinib, after which we analyzed bronchoalveolar lavage fluid (BALF) for inflammatory cytokines (IL-6, IL-8, IP-10, IL-2) and CXCL12 levels via ELISA. Additionally, in vitro experiments were performed using the murine lung epithelial cell line MLE-12 to assess the combined effects of Tofacitinib and a CXCR4 inhibitor on key inflammatory signaling pathways (JAK-STAT and NF-κB) through Western blot analysis.</div></div><div><h3>Results</h3><div>Clinical analysis revealed that children with SMPP had significantly prolonged fever duration (<em>P</em> = 0.0062), extended hospitalization (<em>P</em> < 0.0001), elevated erythrocyte sedimentation rate (<em>P</em> = 0.0161), and higher proportions of CD4<sup>+</sup>CXCR4<sup>+</sup> T lymphocytes (<em>P</em> < 0.0001) compared to Non-severe MPP patients. However, no statistically significant differences were observed in serum levels of C-reactive protein, procalcitonin, or lactate dehydrogenase between the two groups. In the MPP mouse model, BALF analysis demonstrated marked increases in pro-inflammatory cytokines (IL-6, IL-8, IP-10, IL-2) and CXCL12 (<em>P</em> < 0.05), all of which were significantly attenuated by Tofacitinib treatment. Furthermore, Tofacitinib administration reduced CXCR4 expression on CD4<sup>+</sup> T cells in lung tissues. In vitro experiments confirmed that the combination of Tofacitinib and a CXCR4 inhibitor synergistically suppressed activation of the JAK-STAT and NF-κB pathways.</div></div><div><h3>Conclusion</h3><div>Our findings indicate that elevated CD4<sup>+</sup>CXCR4<sup>+</sup> T cell proportions may serve as a predictive biomarker for disease seve

目的：本研究有两个主要目的。首先，我们的目的是研究趋化因子受体CXCR4在CD4+ T淋巴细胞上的差异表达是否可以作为儿童重症肺炎支原体肺炎（SMPP）患者与非重症肺炎支原体肺炎患者之间的区别免疫特征。其次，我们通过建立MPP动物模型，通过临床观察和实验验证，研究JAK抑制剂Tofacitinib对CXCR4通路调节的影响，探索其在MPP中的治疗潜力。方法：我们开展了一项前瞻性队列研究，纳入了2023年至2024年在嘉定区中心医院诊断为MPP的267例儿科患者，其中42例为SMPP， 225例为非重度MPP。入院24小时内系统收集基线临床和实验室参数。采用流式细胞术定量外周血样本中表达CXCR4的CD4+ T细胞（CD4+CXCR4+）的百分比。为了进行机制研究，我们建立了小鼠MPP模型，以评价托法替尼的免疫调节作用。治疗组分别给予对照或托法替尼，之后通过ELISA分析支气管肺泡灌洗液（BALF）中炎症因子（IL-6、IL-8、IP-10、IL-2）和CXCL12水平。此外，利用小鼠肺上皮细胞系MLE-12进行体外实验，通过Western blot分析Tofacitinib和CXCR4抑制剂联合使用对关键炎症信号通路（JAK-STAT和NF-κB）的影响。结果：临床分析显示，SMPP患儿发热时间明显延长（P = 0.0062），住院时间明显延长（P +CXCR4+ T淋巴细胞）。体外实验证实，Tofacitinib与CXCR4抑制剂联合使用可协同抑制JAK-STAT和NF-κB通路的激活。结论：我们的研究结果表明，CD4+CXCR4+ T细胞比例升高可能是儿童MPP疾病严重程度的预测性生物标志物。实验数据表明，Tofacitinib通过调节CXCL12/CXCR4轴对MPP产生保护作用，导致炎症细胞因子的产生减少。观察到的JAK-STAT和NF-κB信号通路的抑制为Tofacitinib在MPP治疗中的潜在治疗应用提供了机制支持，无论是单独使用还是与CXCR4抑制剂联合使用。需要进一步的临床研究来验证这些发现，并评估这种治疗策略的转化潜力。

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