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miR-141-3p attenuates inflammation and oxidative stress-induced pulmonary fibrosis in ARDS via the Keap1/Nrf2/ARE signaling pathway. miR-141-3p 通过 Keap1/Nrf2/ARE 信号通路减轻炎症和氧化应激诱导的 ARDS 肺纤维化
IF 3.3 4区 医学 Q3 IMMUNOLOGY Pub Date : 2024-10-01 Epub Date: 2024-06-12 DOI: 10.1007/s12026-024-09503-7
Guangwen Long, Qian Zhang, Xiulin Yang, Hongpeng Sun, Chunling Ji

The present research aimed to investigate the effects and mechanisms of microRNA (miR)-141-3p on pulmonary fibrosis of acute respiratory distress syndrome (ARDS). A rat ARDS model was established by the intratracheal drip of 10 mg/kg lipopolysaccharide (LPS). miR-141-3p and Kelch-like ECH-associated protein 1 (Keap1) expression was detected using RT-qPCR assay. Inflammatory factors in bronchoalveolar lavage fluid (BALF) and lung tissues were measured with enzyme-linked immunosorbent assay (ELISA). Lung fibrosis was evaluated using Masson's trichrome staining and hydroxyproline assay kits. Tissue oxidative stress marker levels were assessed by a commercial kit. Protein variations in the EMT pathway and Keap1/nuclear factor-erythroid 2-related factor 2 (Nrf2)/antioxidant response element (ARE) pathway were investigated by Western blot analysis. Targeting relationship verified by dual-luciferase reporter assay. The expression of miR-141-3p was significantly upregulated in LPS-induced ARDS rats, while Keap1 was downregulated. Overexpression of miR-141-3p decreased the levels of tumor necrosis factor (TNF)-α, interleukin (IL)-1β, IL-6, superoxide dismutase (SOD), and glutathione (GSH) while elevating malondialdehyde (MDA) expression in LPS-induced ARDS rats. Elevation of miR-141-3p reduced fibrosis scores, enhanced E-cadherin protein expression, and decreased vimentin and α-SMA protein expression in LPS-induced ARDS rats. This elevation of miR-141-3p also upregulated Nrf2, heme oxygenase-1 (HO-1), and NAD(P)H:quinone oxido-reductase-1 (NQO1) proteins levels. Moreover, Keap1 overexpression reversed the inhibitory effects of miR-141-3p on LPS-triggered inflammation, oxidative stress, and fibrosis. miR-141-3p may attenuate inflammation and oxidative stress-induced pulmonary fibrosis in ARDS via the Keap1/Nrf2/ARE signaling pathway. Our study provides new ideas for the treatment of ARDS.

本研究旨在探讨microRNA(miR)-141-3p对急性呼吸窘迫综合征(ARDS)肺纤维化的影响和机制。通过气管内滴加 10 毫克/千克脂多糖(LPS)建立大鼠 ARDS 模型,采用 RT-qPCR 法检测 miR-141-3p 和 Kelch 样 ECH 相关蛋白 1(Keap1)的表达。支气管肺泡灌洗液(BALF)和肺组织中的炎症因子用酶联免疫吸附试验(ELISA)测定。使用马森三色染色法和羟脯氨酸检测试剂盒对肺纤维化进行评估。组织氧化应激标记物水平由商用试剂盒进行评估。通过Western印迹分析研究了EMT通路和Keap1/核因子-红细胞2相关因子2(Nrf2)/抗氧化反应元件(ARE)通路的蛋白质变化。通过双荧光素酶报告实验验证了靶向关系。在 LPS 诱导的 ARDS 大鼠中,miR-141-3p 的表达明显上调,而 Keap1 则下调。在 LPS 诱导的 ARDS 大鼠中,miR-141-3p 的过表达降低了肿瘤坏死因子(TNF)-α、白细胞介素(IL)-1β、IL-6、超氧化物歧化酶(SOD)和谷胱甘肽(GSH)的水平,同时升高了丙二醛(MDA)的表达。在 LPS 诱导的 ARDS 大鼠体内,miR-141-3p 的升高降低了纤维化评分,增强了 E-cadherin 蛋白表达,降低了波形蛋白和 α-SMA 蛋白表达。miR-141-3p 的升高还上调了 Nrf2、血红素加氧酶-1(HO-1)和 NAD(P)H:quinone 氧化还原酶-1(NQO1)蛋白的水平。此外,Keap1的过表达逆转了miR-141-3p对LPS诱发的炎症、氧化应激和纤维化的抑制作用。 miR-141-3p可能通过Keap1/Nrf2/ARE信号通路减轻炎症和氧化应激诱发的ARDS肺纤维化。我们的研究为治疗 ARDS 提供了新思路。
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引用次数: 0
The impact of BDNF and CD4 + T cell crosstalk on depression. BDNF 和 CD4 + T 细胞串联对抑郁症的影响。
IF 3.3 4区 医学 Q3 IMMUNOLOGY Pub Date : 2024-10-01 Epub Date: 2024-07-09 DOI: 10.1007/s12026-024-09514-4
Michel-Edwar Mickael, Norwin Kubick, Małgorzata Dragan, Atanas G Atanasov, Michał Ławiński, Justyna Paszkiewicz, Jarosław Olav Horbańczuk, Piotr Religa, Ana Thorne, Mariusz Sacharczuk
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引用次数: 0
A rare cause of immune dysregulation, prolidase deficiency: a case report and review of the literature 免疫失调的罕见病因--普罗利酶缺乏症:病例报告和文献综述
IF 4.4 4区 医学 Q3 IMMUNOLOGY Pub Date : 2024-09-19 DOI: 10.1007/s12026-024-09541-1
Damla Baysal Bakır, Suna Asilsoy, Nevin Uzuner, Halime Yağmur, Gizem Kabadayı, Rüya Torun, Zehra Kızıldağ Karabacak, Esra Işık, Suzan Süncak

We report a pediatric patient with prolidase deficiency, caused by a mutation in the PEPD gene, which encodes the enzyme prolidase D, with a lupus-like clinic and marked dysmorphic features along with pulmonary, neurological, skeletal, and immune system involvement. In addition to being the first known case in the literature where Friedrich’s ataxia and prolidase deficiency were observed together, we aimed to highlight that this diagnosis should be considered in patients with autoimmunity and additional systemic findings such as treatment-resistant skin lesions, intellectual disability, and pulmonary manifestations. Furthermore, we sought to compare this case with others documented in the literature.

我们报告了一名普利苷酶缺乏症的儿科患者,该患者是由编码普利苷酶 D 的 PEPD 基因突变引起的,具有狼疮样临床表现和明显的畸形特征,并伴有肺部、神经系统、骨骼和免疫系统受累。这是文献中首例同时出现弗里德里希共济失调症和普利酶缺乏症的病例,此外,我们还希望强调,如果患者伴有自身免疫和其他系统性表现,如耐药性皮肤损伤、智力障碍和肺部表现,则应考虑这一诊断。此外,我们还试图将该病例与文献中记载的其他病例进行比较。
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引用次数: 0
Patent blue V dye anaphylaxis: should basophil activation test play a role in the diagnosis? 专利蓝 V 染色剂过敏性休克:嗜碱性粒细胞活化测试是否应在诊断中发挥作用?
IF 4.4 4区 医学 Q3 IMMUNOLOGY Pub Date : 2024-09-18 DOI: 10.1007/s12026-024-09542-0
Ana Raquel Pinto, André Justino Alberto, Esmeralda Neves, Fabrícia Carolino
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引用次数: 0
DMRT3-mediated lncRNA OIP5-AS1 promotes the pyroptosis of bronchial epithelial cells by binding with EIF4A3 to enhance YAP mRNA stability DMRT3介导的lncRNA OIP5-AS1通过与EIF4A3结合增强YAP mRNA的稳定性,从而促进支气管上皮细胞的脓毒症
IF 4.4 4区 医学 Q3 IMMUNOLOGY Pub Date : 2024-09-17 DOI: 10.1007/s12026-024-09534-0
Yunchan Liu, Yamei Zheng, Chaochao Wei, Xingjun Cai

Asthma is featured by persistent airway inflammation. Long noncoding RNAs (lncRNAs) are reported to play critical roles in asthma. However, the function of Opa interacting protein 5-antisense 1 (OIP5-AS1) in pyroptosis during the development of asthma remains unexplored. The blood samples of asthma patients (n = 32) as well as the baseline characteristics of asthma patients or healthy people were collected. An in vivo model of asthma was established using house dust mites (HDM). To mimic asthma in vitro, BEAS-2B cells were treated with HDM. Cell pyroptosis and apoptosis were examined by flow cytometry. The levels of interleukin-1 beta (IL-1β) and interleukin-18 (IL-18) were detected by enzyme-linked immunosorbent assay (ELISA). The binding among messenger RNAs (mRNAs) was assessed by chromatin immunoprecipitation (ChIP), dual luciferase report assay, RNA immunoprecipitation (RIP), co-immunoprecipitation (Co-IP), and RNA pull-down assay, respectively. The cellular localization was observed by fluorescence in situ hybridization (FISH) staining. The level of OIP5-AS1 was upregulated in asthma patients. HDM induced pyroptosis and increased the levels of IL-18, IL-1β, and lactate dehydrogenase (LDH) in BEAS-2B cells, which was obviously reversed by OIP5-AS1 knockdown. Consistently, the expressions of NOD-like receptor protein 3 (NLRP3), apoptosis-associated speck-like protein containing a caspase recruitment domain (ASC), c-caspase 1, and pyroptosis-related gasdermin D-1 (GSDMD-1) in BEAS-2B cells were upregulated by HDM treatment, while these phenomena were partially abolished by silencing of OIP5-AS1. Moreover, HDM promoted the progression of asthma in vivo, which was rescued by the downregulation of OIP5-AS1. OIP5-AS1 silencing decreased HDM-induced cell pyroptosis by inactivation of NLRP3. More importantly, OIP5-AS1 promoted the mRNA stability of yes-associated protein (YAP) via binding with eukaryotic translation initiation factor 4A3 (EIF4A3), and OIP5-AS1 was transcriptionally upregulated by doublesex and mab-3 related transcription factor 3 (DMRT3). DMRT3-mediated OIP5-AS1 aggravated the progression of asthma by mediation of the EIF4A3/YAP axis, which might provide a new therapeutic strategy against asthma.

哮喘的特点是持续的气道炎症。据报道,长非编码 RNA(lncRNA)在哮喘中发挥着关键作用。然而,Opa互作蛋白5-反义1(OIP5-AS1)在哮喘发病过程中的热变性功能仍未得到研究。研究人员收集了哮喘患者(32 人)的血液样本以及哮喘患者或健康人的基线特征。利用屋尘螨(HDM)建立了哮喘的体内模型。为了在体外模拟哮喘,用 HDM 处理 BEAS-2B 细胞。流式细胞术检测了细胞的热解和凋亡。酶联免疫吸附试验(ELISA)检测了白细胞介素-1β(IL-1β)和白细胞介素-18(IL-18)的水平。分别通过染色质免疫沉淀(ChIP)、双荧光素酶报告实验、RNA免疫沉淀(RIP)、共免疫沉淀(Co-IP)和 RNA 下拉实验来评估信使 RNA(mRNA)之间的结合。荧光原位杂交(FISH)染色观察细胞定位。在哮喘患者中,OIP5-AS1的水平上调。HDM诱导BEAS-2B细胞发生热休克,并增加IL-18、IL-1β和乳酸脱氢酶(LDH)的水平,而敲除OIP5-AS1可明显逆转这一现象。同样,HDM处理后,BEAS-2B细胞中的NOD样受体蛋白3(NLRP3)、含caspase募集结构域的凋亡相关斑点样蛋白(ASC)、c-caspase 1和与热凋亡相关的gasdermin D-1(GSDMD-1)的表达上调,而沉默OIP5-AS1后这些现象部分消失。此外,HDM促进了哮喘在体内的发展,而下调OIP5-AS1则可缓解这一现象。通过使 NLRP3 失活,OIP5-AS1 的沉默减少了 HDM 诱导的细胞脓毒症。更重要的是,OIP5-AS1通过与真核翻译起始因子4A3(EIF4A3)结合,促进了是相关蛋白(YAP)的mRNA稳定性。DMRT3介导的OIP5-AS1通过EIF4A3/YAP轴的中介作用加剧了哮喘的恶化,这可能为哮喘提供了一种新的治疗策略。
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引用次数: 0
ASIA syndrome after BNT162b2 vaccination: Is it a distinct rheumatoid arthritis phenotype? 接种 BNT162b2 疫苗后的 ASIA 综合征:它是一种独特的类风湿性关节炎表型吗?
IF 4.4 4区 医学 Q3 IMMUNOLOGY Pub Date : 2024-09-16 DOI: 10.1007/s12026-024-09540-2
Mete Pekdiker, Sertaç Ketenci

Vaccines are an identified cause of autoimmune/inflammatory syndrome induced by adjuvants (ASIA syndrome). In this research, we aimed to investigate the remarkable features of patients, whom we classified as ASIA syndrome, developing rheumatoid arthritis (RA) after BNT162b2 vaccination. Patients who were asymptomatic before the BNT162b2 vaccination, developed chronic arthritis within 3 months after the vaccination, and fulfilled the 2010 American College of Rheumatology/European League Against Rheumatism RA classification criteria were enrolled in the study. Demographic, laboratory, clinical, and treatment characteristics were reviewed retrospectively. We identified ten patients developing RA following BNT162b2 vaccination. The median age was 54.5 years and six of them were female. The median time between vaccination and onset of symptoms was 7 days; seven patients had acute arthritis, and four had intermittent arthritis at the onset of the disease. Only three patients had a disease onset in the small joints of the hands. All patients had radiological erosions on hand X-rays. We reported a case series of patients, classifiable as having ASIA syndrome, who developed RA with radiological erosions after the BNT162b2 vaccine. The onset of the disease in joints different from the typically expected ones, along with the early development of erosions in hand X-rays, suggests that these cases may follow a course distinct from classic RA. RA that develops following mRNA vaccination may have an aggressive course, but studies with larger sample sizes are needed.

疫苗是佐剂诱导的自身免疫/炎症综合征(ASIA 综合征)的一个公认病因。在这项研究中,我们旨在调查被归类为 ASIA 综合征的患者在接种 BNT162b2 疫苗后出现类风湿性关节炎(RA)的显著特征。研究招募了接种 BNT162b2 疫苗前无症状、接种疫苗后 3 个月内出现慢性关节炎并符合 2010 年美国风湿病学会/欧洲抗风湿病联盟 RA 分类标准的患者。我们对患者的人口统计学特征、实验室特征、临床特征和治疗特征进行了回顾性分析。我们发现有 10 名患者在接种 BNT162b2 疫苗后出现了 RA。中位年龄为 54.5 岁,其中 6 人为女性。从接种疫苗到出现症状的中位时间为 7 天;7 名患者出现急性关节炎,4 名患者在发病时出现间歇性关节炎。只有三名患者的发病部位是手部小关节。所有患者的手部 X 光片均有放射性侵蚀。我们报告了一系列可归类为ASIA综合征的患者病例,他们在接种BNT162b2疫苗后出现了伴有放射性侵蚀的RA。发病关节与通常预期的关节不同,而且手部X光片早期出现侵蚀,这表明这些病例的病程可能有别于典型的RA。接种mRNA疫苗后出现的RA病程可能具有侵袭性,但还需要进行样本量更大的研究。
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引用次数: 0
Serum soluble interleukin-2 receptor alpha may predict tubulointerstitial inflammatory cell infiltration and short-term disease progression in immunoglobin A nephropathy 血清可溶性白细胞介素-2 受体α可预测免疫球蛋白 A 肾病的肾小管间质炎症细胞浸润和短期病情进展
IF 4.4 4区 医学 Q3 IMMUNOLOGY Pub Date : 2024-09-14 DOI: 10.1007/s12026-024-09533-1
Chenqi Xu, Kunming Pan, Jie Li, Yang Li, Shi Jin, Yiqin Shi, Jie Teng, Xiaoqiang Ding, Xialian Xu, Hong Liu

This study aims to explore the relationship between serum soluble interleukin-2 receptor alpha (sIL-2Rα) levels and histologic features in immunoglobin A nephropathy (IgAN), and evaluate its predicting values on disease progression and remission status. IgAN patients were included retrospectively. Lee classification, Oxford classification and histological scoring were evaluated. Patients’ estimated filtration rate (eGFR) and proteinuria remission status were collected during 6-month follow-up. Logistic regression was used to determine the risk factors and predicting value. Receiver operating characteristic (ROC) curve were used to determine the predicting value for outcome. One hundred seventy-two subjects were included in this study. Individuals in moderate-to-severe tubulointerstitial inflammatory cell infiltration group manifested with significantly elevated serum sIL-2Rα levels than those in non-to-mild group. Serum sIL-2Rα levels were positively correlated with infiltration scores. Serum sIL-2Rα was an independent risk factor for moderate-to-severe inflammatory cell infiltration [sIL-2Rα: OR 1.29 (1.015–1.640, p = 0.038)]. ROC curve analysis regarding predictive value for moderate-to-severe inflammatory cell infiltration of sIL-2Rα suggested area under curve was 0.859 (0.801–0.918, p = 0.000) when sIL-2Rα combined with eGFR < 60 mL/(min·1.73 m2), 24-h proteinuria excretion > 1.0 g, and hemoglobin. It showed good sensitivity (71.6%) and specificity (87.6%). Additionally, sIL-2Rα levels at kidney biopsy were strong predictive factor for kidney function loss 6 months after kidney biopsy [OR 4.161 (1.013–17.088, p = 0.048)]. High serum sIL-2Rα was significantly associated with serious inflammatory cell infiltration in IgAN, and it showed strong predictive value for disease prognosis. Serum sIL-2Rα could be a useful noninvasive biomarker to evaluate the extent of histological injury and disease prognosis in IgAN.

本研究旨在探讨血清可溶性白细胞介素-2受体α(sIL-2Rα)水平与免疫球蛋白A肾病(IgAN)组织学特征之间的关系,并评估其对疾病进展和缓解状态的预测价值。IgAN患者均为回顾性纳入。对李氏分类法、牛津分类法和组织学评分进行了评估。在6个月的随访中收集了患者的估计滤过率(eGFR)和蛋白尿缓解状态。采用逻辑回归法确定风险因素和预测值。采用接收者操作特征曲线(ROC)确定结果的预测值。本研究共纳入 172 名受试者。与非轻度组相比,中重度肾小管间质炎症细胞浸润组患者的血清 sIL-2Rα 水平明显升高。血清 sIL-2Rα 水平与浸润评分呈正相关。血清 sIL-2Rα 是中度至重度炎症细胞浸润的独立危险因素[sIL-2Rα:OR 1.29 (1.015-1.640, p = 0.038)]。当 sIL-2Rα 与 eGFR < 60 mL/(min-1.73 m2)、24 小时蛋白尿排泄量 > 1.0 g 和血红蛋白相结合时,sIL-2Rα 对中重度炎症细胞浸润的预测价值的 ROC 曲线分析表明曲线下面积为 0.859 (0.801-0.918, p = 0.000)。它显示出良好的灵敏度(71.6%)和特异性(87.6%)。此外,肾活检时的 sIL-2Rα 水平是肾活检后 6 个月肾功能丧失的有力预测因素[OR 4.161 (1.013-17.088, p = 0.048)]。高血清 sIL-2Rα 与 IgAN 严重的炎症细胞浸润显著相关,对疾病预后有很强的预测价值。血清sIL-2Rα可能是评估IgAN组织学损伤程度和疾病预后的一种有用的非侵入性生物标志物。
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引用次数: 0
Tumour-associated macrophages in diffuse large B-cell lymphoma: the prognostic and therapeutic impact in a South African centre with high HIV seroprevalence 弥漫性大 B 细胞淋巴瘤中的肿瘤相关巨噬细胞:在南非一个艾滋病毒高血清流行中心对预后和治疗的影响
IF 4.4 4区 医学 Q3 IMMUNOLOGY Pub Date : 2024-09-11 DOI: 10.1007/s12026-024-09537-x
Jenifer Vaughan, Tracey Wiggill, Zainab Mia, Moosa Patel

Diffuse large B-cell lymphoma (DLBCL) is a common malignancy among people living with HIV. Macrophage enrichment of the tumour microenvironment (TME) is a prognostic factor in DLBCL among immunocompetent people, with some studies reporting that macrophage enrichment predicts a superior response to rituximab therapy. The macrophage phenotype is also important, with reportedly poorer outcomes with enrichment of anti-inflammatory (M2) macrophages. To date, the relationship between the type/number of tumour macrophages and outcomes in HIV-associated DLBCL (HIV-DLBCL) has been poorly explored. In this study, we assessed tumour macrophage numbers in a South African cohort of patients with DLBCL and a high HIV-seropositivity rate. Immunohistochemistry for CD68 and CD163 was performed on the diagnostic biopsies of 79 patients with DLBCL. Relevant information was documented from the clinical records, including disease stage, international-prognostic index score, HIV-related parameters, C-reactive protein, ferritin levels and immune cell numbers (monocytes, lymphocytes and neutrophils). Survival analysis was performed using Kaplan–Meier survival estimates, and the correlation between tumour macrophage numbers and a variety of immunological parameters was assessed using Spearman’s rho. Of the 79 patients included, 87.2% were living with HIV, and rituximab therapy was used in 46.9%. Tumour macrophage numbers were not related to HIV status, but low pro-inflammatory (M1) macrophage numbers (CD68 + CD163 −) were significantly associated with poorer outcomes (HR 2.02, p = 0.03). M2 macrophage (CD68 + CD163 +) enrichment was not predictive of survival but was associated with improved response to rituximab therapy (HR 0.19; p = 0.002). Macrophage numbers were marginally correlated with ferritin levels, which showed modest performance as a peripheral blood biomarker of the TME macrophage status (AUC 0.6 at a level of 374 µg/L), and high ferritin levels were associated with a superior response to rituximab-therapy (HR 0.28, p = 0.034). Pro-inflammatory macrophages are important in tumour control in HIV-DLBCL, while M2 macrophage enrichment improves the response to rituximab therapy. Ferritin shows promise as a biomarker for identifying patients more likely to benefit from rituximab therapy.

弥漫大 B 细胞淋巴瘤(DLBCL)是 HIV 感染者中常见的恶性肿瘤。肿瘤微环境(TME)中巨噬细胞的富集是免疫功能正常者患弥漫性大B细胞淋巴瘤的一个预后因素,一些研究报告称,巨噬细胞的富集预示着对利妥昔单抗治疗的良好反应。巨噬细胞的表型也很重要,据报道,抗炎(M2)巨噬细胞富集的患者预后较差。迄今为止,人们对肿瘤巨噬细胞的类型/数量与艾滋病相关DLBCL(HIV-DLBCL)预后之间的关系还缺乏深入研究。在这项研究中,我们评估了南非队列中DLBCL患者的肿瘤巨噬细胞数量以及HIV血清阳性率。我们对79名DLBCL患者的诊断性活检组织进行了CD68和CD163免疫组化。临床记录中记录了相关信息,包括疾病分期、国际预后指数评分、HIV相关参数、C反应蛋白、铁蛋白水平和免疫细胞数量(单核细胞、淋巴细胞和中性粒细胞)。生存分析采用卡普兰-梅耶生存估计值,肿瘤巨噬细胞数量与各种免疫学参数之间的相关性采用斯皮尔曼rho进行评估。在纳入的79名患者中,87.2%是艾滋病毒携带者,46.9%使用了利妥昔单抗治疗。肿瘤巨噬细胞数量与艾滋病病毒感染状况无关,但低促炎性(M1)巨噬细胞数量(CD68 + CD163 -)与较差的预后显著相关(HR 2.02,p = 0.03)。M2巨噬细胞(CD68 + CD163 +)的富集不能预测生存率,但与利妥昔单抗治疗反应的改善有关(HR 0.19; p = 0.002)。巨噬细胞数量与铁蛋白水平略有相关,铁蛋白作为TME巨噬细胞状态的外周血生物标志物表现一般(在374微克/升的水平上,AUC为0.6),高铁蛋白水平与利妥昔单抗治疗的良好反应相关(HR 0.28,p = 0.034)。促炎性巨噬细胞对HIV-DLBCL的肿瘤控制非常重要,而M2巨噬细胞的富集可改善对利妥昔单抗疗法的反应。铁蛋白有望成为一种生物标志物,用于识别更有可能从利妥昔单抗治疗中获益的患者。
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引用次数: 0
Changes in immune subsets during chemotherapy as prognosis biomarkers for multiple myeloma patients by longitudinal monitoring 通过纵向监测将化疗期间免疫亚群的变化作为多发性骨髓瘤患者预后的生物标志物
IF 4.4 4区 医学 Q3 IMMUNOLOGY Pub Date : 2024-09-10 DOI: 10.1007/s12026-024-09521-5
Pengcheng Xu, Ying Li, Xibing Zhuang, Lei Yue, Yanna Ma, Wenjin Xue, Lili Ji, Yanxia Zhan, Yang Ou, Tiankui Qiao, Duojiao Wu, Peng Liu, Hao Chen, Yunfeng Cheng

Multiple myeloma (MM) is a malignancy of plasma cells accompanied by immune dysfunction. This study aimed to provide a comprehensive and dynamic characterization of the peripheral immune environment in MM patients and find its diagnostic and prognostic values for therapy. The peripheral immune profiles of MM inpatients and healthy controls were assessed by flow cytometry. A longitudinal study of immune subsets was observed during cycles of chemotherapy. The diagnostic and prognostic models were established based on immune subsets by the absolute shrinkage and selection operator (LASSO) and multivariate regression. MM patients possessed an impeded immune landscape, including reduced activation of B cells, increased effective T cells and regulatory T cells (Tregs), augmented CD16 expression on monocytes and dendritic cell percentages, decreased CD56dimCD16+ natural killer cells (NKs), and amplified CD56bright and HLA-DR+ natural killer T cells (NKTs). Chemotherapy has different dynamic effects on specific cells, of which 2 cycles is the key turning point. NKT, dendritic cells, naïve Tc and Th cells, HLA-DR+ Tc cells, CD56dim NKTs, CD16++ monocytes, and CD25+ B cells could have the diagnostic value, and a prognostic model including neutrophils, naïve Tc cells, CD56brightCD16dim NKs, and CD16+ dendritic cells was established with acceptable accuracy. Our data showed dynamic and abnormal peripheral immune profiles in MM patients, which had prognostic values and could provide the basis for clinical therapy.

多发性骨髓瘤(MM)是一种伴有免疫功能障碍的浆细胞恶性肿瘤。本研究旨在全面、动态地描述多发性骨髓瘤患者的外周免疫环境,并发现其对治疗的诊断和预后价值。通过流式细胞术评估了 MM 住院患者和健康对照组的外周免疫特征。在化疗周期中对免疫亚群进行了纵向研究。通过绝对缩小和选择算子(LASSO)和多元回归法,建立了基于免疫亚群的诊断和预后模型。MM患者的免疫功能受损,包括B细胞活化减少、有效T细胞和调节性T细胞(Tregs)增加、单核细胞和树突状细胞CD16表达增加、CD56dimCD16+自然杀伤细胞(NKs)减少、CD56bright和HLA-DR+自然杀伤T细胞(NKTs)增加。化疗对特定细胞有不同的动态影响,其中两个周期是关键的转折点。NKT、树突状细胞、幼稚Tc和Th细胞、HLA-DR+ Tc细胞、CD56dim NKTs、CD16++单核细胞和CD25+ B细胞具有诊断价值,建立的预后模型包括中性粒细胞、幼稚Tc细胞、CD56brightCD16dim NKs和CD16+树突状细胞,其准确性可以接受。我们的数据显示了MM患者外周免疫谱的动态和异常,这些数据具有预后价值,可为临床治疗提供依据。
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引用次数: 0
Chronic hyperglycemia impairs anti-microbial function of macrophages in response to Mycobacterium tuberculosis infection. 慢性高血糖会损害巨噬细胞对结核分枝杆菌感染的抗微生物功能。
IF 3.3 4区 医学 Q3 IMMUNOLOGY Pub Date : 2024-08-01 Epub Date: 2024-02-12 DOI: 10.1007/s12026-024-09462-z
Gaurav Kumar Chaubey, Radheshyam Modanwal, Rahul Dilawari, Sharmila Talukdar, Asmita Dhiman, Surbhi Chaudhary, Anil Patidar, Chaaya Iyengar Raje, Manoj Raje

Diabetes mellitus (DM) is a major risk factor for tuberculosis (TB), though the underlying mechanisms linking DM and TB remain ambiguous. Macrophages are a key player in the innate immune response and their phagocytic ability is enhanced in response to microbial infections. Upon infection or inflammation, they also repel invading pathogens by generating; reactive oxygen species (ROS), reactive nitrogen species (RNS), pro-inflammatory cytokines (IL-1β and IL-6), and anti-inflammatory cytokines (IL-10). However, the robustness of these innate defensive capabilities of macrophages when exposed to hyperglycemia remains unclear. In our current work, we explored the production of these host defense molecules in response to challenge with Mycobacterium tuberculosis (Mtb) infection and lipopolysaccharide (LPS) stimulation. Utilizing peritoneal macrophages from high-fat diet + streptozotocin induced diabetic mice and hyperglycemic THP-1-derived macrophages as model systems; we found that LPS stimulation and Mtb infection were ineffective in stimulating the production of ROS, RNS, and pro-inflammatory cytokines in cells exposed to hyperglycemia. On the contrary, an increase in production of anti-inflammatory cytokines was observed. To confirm the mechanism of decreased anti-bacterial activity of the diabetic macrophage, we explored activation status of these compromised macrophages and found decreased surface expression of activation (TLR-4) and differentiation markers (CD11b and CD11c). We postulate that this could be the cause for higher susceptibility for Mtb infection among diabetic individuals.

糖尿病(DM)是结核病(TB)的一个主要风险因素,但糖尿病与结核病之间的内在联系机制仍不明确。巨噬细胞是先天性免疫反应中的关键角色,其吞噬能力在微生物感染时会增强。在感染或发炎时,巨噬细胞还会产生活性氧(ROS)、活性氮(RNS)、促炎细胞因子(IL-1β 和 IL-6)和抗炎细胞因子(IL-10),从而击退入侵的病原体。然而,巨噬细胞在暴露于高血糖时的这些先天防御能力是否强大仍不清楚。在目前的研究中,我们探讨了这些宿主防御分子在结核分枝杆菌(Mtb)感染和脂多糖(LPS)刺激下产生的反应。利用高脂饮食+链脲佐菌素诱导的糖尿病小鼠腹腔巨噬细胞和高血糖 THP-1 衍生巨噬细胞作为模型系统,我们发现 LPS 刺激和 Mtb 感染不能有效刺激暴露于高血糖的细胞产生 ROS、RNS 和促炎细胞因子。相反,却观察到抗炎细胞因子的产生增加。为了证实糖尿病巨噬细胞抗菌活性降低的机制,我们研究了这些受损巨噬细胞的活化状态,发现活化(TLR-4)和分化标志物(CD11b 和 CD11c)的表面表达降低。我们推测,这可能是糖尿病患者更易感染 Mtb 的原因。
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Immunologic Research
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