Journal of Leukocyte Biology最新文献

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Enhanced Siglec-8 and HLA-DR and Reduced CRTH2 Surface Expression, Highlight a Distinct Phenotypic Signature of Circulating Eosinophils in Atopic Dermatitis.
IF 3.6 3区 医学
Journal of Leukocyte Biology Pub Date : 2025-02-25 DOI: 10.1093/jleuko/qiaf023
Frédéric Dezoteux, Pierre Marcant, Arnaud Dendooven, Émeline Delaunay, Stéphane Esnault, Jacques Trauet, Guillaume Lefevre, Delphine Staumont-Salle
{"title":"Enhanced Siglec-8 and HLA-DR and Reduced CRTH2 Surface Expression, Highlight a Distinct Phenotypic Signature of Circulating Eosinophils in Atopic Dermatitis.","authors":"Frédéric Dezoteux, Pierre Marcant, Arnaud Dendooven, Émeline Delaunay, Stéphane Esnault, Jacques Trauet, Guillaume Lefevre, Delphine Staumont-Salle","doi":"10.1093/jleuko/qiaf023","DOIUrl":"https://doi.org/10.1093/jleuko/qiaf023","url":null,"abstract":"<p><p>Atopic dermatitis (AD) as well as other type 2 immune response (T2) diseases are often linked to elevated eosinophil (Eos) levels in the blood. Although the role of Eos in AD pathophysiology is suspected, it remains unclear. The development of new treatments targeting the T2 response, particularly cytokines involved in Eos activation and chemotaxis, makes it necessary to identify potential Eos profiles in AD that may respond to these treatments. A prospective study was conducted comparing blood Eos phenotypes in moderate-to-severe AD patients (n=19) without recent systemic treatment to healthy individuals (HI, n=19). The primary outcome was the membranous phenotypic signature of Eos, assessed by flow cytometry. Most AD patients (84%) had early onset in childhood, a severe disease (mean SCORAD of 57.5), and elevated blood Eos counts (310 per µl in AD vs 120 in HI, p<0.0001). AD patients exhibited lower CRTH2 on Eos but higher levels of HLA-DR and Siglec-8 compared to HI. Other surface proteins showed no significant differences. Clustering analysis confirmed increased Siglec-8 in AD patients. Additionally, AD patients had higher serum levels of T2 immune response-markers as eotaxin-2, IL-5, IL-3, and TARC. Circulating Eos in AD patients show a distinct phenotypic profile, suggesting a role in AD pathophysiology and potential involvement in differential treatment responses.</p>","PeriodicalId":16186,"journal":{"name":"Journal of Leukocyte Biology","volume":" ","pages":""},"PeriodicalIF":3.6,"publicationDate":"2025-02-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143492296","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
MiR-340-5p alleviates AECOPD by targeting MAP3K2 via Qingjin Huatan Decoction therapy.
IF 3.6 3区 医学
Journal of Leukocyte Biology Pub Date : 2025-02-20 DOI: 10.1093/jleuko/qiaf021
Mei Zhao, Zhijian Huang, Jinghui Zheng, Wanying Li, Yunqing Zhong, Tun Ouyang
{"title":"MiR-340-5p alleviates AECOPD by targeting MAP3K2 via Qingjin Huatan Decoction therapy.","authors":"Mei Zhao, Zhijian Huang, Jinghui Zheng, Wanying Li, Yunqing Zhong, Tun Ouyang","doi":"10.1093/jleuko/qiaf021","DOIUrl":"https://doi.org/10.1093/jleuko/qiaf021","url":null,"abstract":"<p><p>Chronic obstructive pulmonary disease (COPD) features persistent inflammation and restricted airflow, with acute exacerbations of COPD (AECOPD) significantly worsening patient outcomes. This study aims to explore the role of Qingjin Huatan Decoction (QJHTT) on AECOPD with the syndrome of phlegm-heat obstruction of the lung.AECOPD was induced in male Sprague-Dawley rats using lipopolysaccharide (LPS) and cigarette smoke exposure. Rats were treated with varying doses of QJHTT. miR-340-5p expression was quantified using qPCR. Lung histopathology was assessed with hematoxylin and eosin (HE) staining, and interleukin-6 (IL-6), interleukin-1 beta (IL-1β), and tumor necrosis factor-alpha (TNF-α) were measured by enzyme-linked immunosorbent assay (ELISA).. The effects on cell viability and apoptosis in primary airway epithelial cells were evaluated using Cell Counting Kit-8 (CCK-8) and flow cytometry assays, respectively. The dual-luciferase reporter assay validated the interaction between miR-340-5p and mitogen-activated protein kinase kinase kinase 2 (MAP3K2), and protein expression was analyzed by Western blot.QJHTT improved lung histopathology, reducing inflammatory cell infiltration and alveolar damage. ELISA results showed reduced inflammatory cytokines levels in QJHTT-treated groups (P < 0.05). qPCR analysis demonstrated that QJHTT upregulated miR-340-5p expression (P < 0.05). miR-340-5p mimic enhanced cell viability and reduced apoptosis in primary airway epithelial cells (P < 0.05). Dual-luciferase reporter assay confirmed that miR-340-5p directly targets MAP3K2, leading to its downregulation (P < 0.05). QJHTT exerts therapeutic effects in phlegm-heat obstructing the lung type of AECOPD through upregulating miR-340-5p and inhibiting MAP3K2. This study highlights the QJHTT and miR-340-5p/MAP3K2 pathway for this disease treatment.</p>","PeriodicalId":16186,"journal":{"name":"Journal of Leukocyte Biology","volume":" ","pages":""},"PeriodicalIF":3.6,"publicationDate":"2025-02-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143458292","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
Histones HIST1 genes and tumor infiltrating lymphocytes in a child with gamma delta T cell acute lymphoblastic leukemia by single-cell sequencing.
IF 3.6 3区 医学
Journal of Leukocyte Biology Pub Date : 2025-02-20 DOI: 10.1093/jleuko/qiaf022
Xiao-Hua Luo, Yan Zhu, Xiao-Qin Duan, Wen Peng, Cai-Xia Pei, Li Yang, Qing Li, Min Zhao, Lan Wang
{"title":"Histones HIST1 genes and tumor infiltrating lymphocytes in a child with gamma delta T cell acute lymphoblastic leukemia by single-cell sequencing.","authors":"Xiao-Hua Luo, Yan Zhu, Xiao-Qin Duan, Wen Peng, Cai-Xia Pei, Li Yang, Qing Li, Min Zhao, Lan Wang","doi":"10.1093/jleuko/qiaf022","DOIUrl":"https://doi.org/10.1093/jleuko/qiaf022","url":null,"abstract":"<p><p>Gamma delta T-cell acute lymphoblastic leukemia (γδ T-ALL) represents a rare subset of T-ALL and is correlated with high rates of induction failure, relapse and increased mortality. γδ T-ALL lacks a biologically-informed framework for guiding its classification and treatment strategies. In this report, we detail a case of child with γδ T-ALL who underwent induction chemotherapy and intensification treatment, followed by haploidentical hematopoietic stem cell transplantation. The patient achieved a clinical complete remission and remains minimal residual disease negative with chidamide maintenance post-transplantation. Single-cell RNA sequencing revealed a connection between histones HIST1 genes and gamma delta T-ALL, and identified potential effector functions of γδ T cells in combating this leukemia. This case carries significant implications for managing γδ T-ALL, highlighting the relationship between histone modification patterns and gamma delta tumor infiltrating lymphocytes in γδ T-ALL cells for developing novel therapeutic approaches.</p>","PeriodicalId":16186,"journal":{"name":"Journal of Leukocyte Biology","volume":" ","pages":""},"PeriodicalIF":3.6,"publicationDate":"2025-02-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143458281","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
Yu-Ping-Feng formula: a promising traditional Chinese medicine for the treatment of primary Sjögren's syndrome. 玉屏风散:治疗原发性 Sjögren's 综合征的前景广阔的传统中药。
IF 3.6 3区 医学
Journal of Leukocyte Biology Pub Date : 2025-02-13 DOI: 10.1093/jleuko/qiae193
Haoling Xu, He Song
{"title":"Yu-Ping-Feng formula: a promising traditional Chinese medicine for the treatment of primary Sjögren's syndrome.","authors":"Haoling Xu, He Song","doi":"10.1093/jleuko/qiae193","DOIUrl":"10.1093/jleuko/qiae193","url":null,"abstract":"","PeriodicalId":16186,"journal":{"name":"Journal of Leukocyte Biology","volume":" ","pages":""},"PeriodicalIF":3.6,"publicationDate":"2025-02-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142108193","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
Hederagenin reduces Aβ-induced oxidative damage, decreases Aβ deposition, and promotes cell survival by the P13K/Akt signaling pathway. Hederagenin 可通过 P13 K/Akt 信号通路减少 Aβ 诱导的氧化损伤、减少 Aβ 沉积并促进细胞存活。
IF 3.6 3区 医学
Journal of Leukocyte Biology Pub Date : 2025-02-13 DOI: 10.1093/jleuko/qiae124
Kunpeng Xie, Hao Wang, Xin Yao, Jialin Lv, Qingyu Wang, Yu Zhao, Shuhan Yang, Lipeng Xu, Yuhua Shi, Jiliang Hu, Yaming Shan
{"title":"Hederagenin reduces Aβ-induced oxidative damage, decreases Aβ deposition, and promotes cell survival by the P13K/Akt signaling pathway.","authors":"Kunpeng Xie, Hao Wang, Xin Yao, Jialin Lv, Qingyu Wang, Yu Zhao, Shuhan Yang, Lipeng Xu, Yuhua Shi, Jiliang Hu, Yaming Shan","doi":"10.1093/jleuko/qiae124","DOIUrl":"10.1093/jleuko/qiae124","url":null,"abstract":"<p><p>Alzheimer's disease (AD) is a neurodegenerative disease characterized by memory loss and cognitive impairment. β-Amyloid (Aβ) is one of the typical pathological features of AD, and its accumulation leads to neuronal death from oxidative stress. Here, we found that hederagenin (HG), a natural product, exhibits antitumor, anti-inflammatory, antidepressant, antineurodegenerative biological activities. However, whether HG has anti-Aβ activity remains unclear. Based on the characteristics of HG, it is hypothesized that HG has biological activity against Aβ injury. Therefore, Aβ-injured SH-SY5Y cells were constructed, and the protective effect of HG against Aβ injury was further evaluated using Caenorhabditis elegans. The results showed that HG increased superoxide dismutase activity, effectively reduced Aβ-induced oxidative damage, and reduced apoptosis via the PI3 K/Akt signaling pathway. HG inhibited Aβ deposition and delayed senescence and paralysis in the C. elegans strain, CL4176. HG showed inhibitory effects on Aβ; therefore, more natural active products are expected to be applied in AD therapy.</p>","PeriodicalId":16186,"journal":{"name":"Journal of Leukocyte Biology","volume":" ","pages":""},"PeriodicalIF":3.6,"publicationDate":"2025-02-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141179375","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
Immunomodulatory effects of Yu-Ping-Feng formula on primary Sjögren syndrome: interrogating the T-cell response. 玉屏风散对原发性 Sjögren's 综合征的免疫调节作用:T 细胞反应研究
IF 3.6 3区 医学
Journal of Leukocyte Biology Pub Date : 2025-02-13 DOI: 10.1093/jleuko/qiae155
Sulan Yu, Xinyao Zhou, Ruihua Liu, Xiaoyu Xu, Danbao Ma, Yun Feng, Xiang Lin
{"title":"Immunomodulatory effects of Yu-Ping-Feng formula on primary Sjögren syndrome: interrogating the T-cell response.","authors":"Sulan Yu, Xinyao Zhou, Ruihua Liu, Xiaoyu Xu, Danbao Ma, Yun Feng, Xiang Lin","doi":"10.1093/jleuko/qiae155","DOIUrl":"10.1093/jleuko/qiae155","url":null,"abstract":"<p><p>Ethnopharmacological treatments have shown beneficial effects in the clinical practice of autoimmune disorders. However, the underlying mechanism of immunomodulatory effects remains challenging, given the complicate composition of herbal medicines. Here, we developed an immunological approach to interrogate the T helper cell response. Through data mining, we hypothesized that Chinese medicine formula Yu-Ping-Feng might be a promising candidate for treating primary Sjögren syndrome, a common autoimmune disease manifested by exocrine gland dysfunction. We took advantage of a mouse model of experimental Sjögren syndrome that we previously established for Yu-Ping-Feng formula treatment. Yu-Ping-Feng therapy ameliorated the experimental Sjögren syndrome pathology in mice with active disease, showing improved salivary function and decreased serum levels of autoantibodies. Phenotypic analysis suggested that both effector T and B cells were significantly suppressed. Using coculture assay and adoptive transfer models, we demonstrated that Yu-Ping-Feng formula directly restrained effector/memory T-cell expansion and differentiation into Th17 and T follicular helper cells, the key subsets in experimental Sjögren syndrome pathogenesis. Importantly, we recruited 20 patients with primary Sjögren syndrome and conducted a pilot study of 8-wk therapy of Yu-Ping-Feng formula. Yu-Ping-Feng treatment effectively improved fatigue symptoms and exocrine gland functions, as well as reduced serum IgG/IgA levels, while effector T- and B-cell subsets were significantly decreased. There was a trend of reduction on disease activity, but not statistically significant. Together, our findings suggest a novel approach to assess the immunomodulatory effects of Yu-Ping-Feng formula, which may be favorable for patients with autoimmune disorders.</p>","PeriodicalId":16186,"journal":{"name":"Journal of Leukocyte Biology","volume":" ","pages":""},"PeriodicalIF":3.6,"publicationDate":"2025-02-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141476751","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
Human endogenous retrovirus-H long terminal repeat-associating 2: an emerging immune checkpoint for cancer immunotherapy. HHLA2:癌症免疫疗法的新兴免疫检查点
IF 3.6 3区 医学
Journal of Leukocyte Biology Pub Date : 2025-02-13 DOI: 10.1093/jleuko/qiae158
Zeya Cao, Youping Wang, Shih-Chin Cheng, Nanhai He
{"title":"Human endogenous retrovirus-H long terminal repeat-associating 2: an emerging immune checkpoint for cancer immunotherapy.","authors":"Zeya Cao, Youping Wang, Shih-Chin Cheng, Nanhai He","doi":"10.1093/jleuko/qiae158","DOIUrl":"10.1093/jleuko/qiae158","url":null,"abstract":"<p><p>Human endogenous retrovirus-H long terminal repeat-associating 2 (HHLA2), a member of the B7 family of co-signaling molecules, is aberrantly expressed in various human cancers and has emerged as a promising target for cancer immunotherapy. It exhibits a unique structure and tissue distribution pattern compared to other B7 family members, where its expression is regulated by the complex physiological and tumor microenvironment. HHLA2 plays a crucial but contradictory role in immune modulation and is thereby associated with heterogeneous prognostic implications across different cancer types. It interacts with two distinct receptors: transmembrane and immunoglobulin domain-containing 2 (TMIGD2), which is predominantly expressed on naïve T and natural killer (NK) cells to deliver co-stimulatory signals to T cells and NK cells, and killer cell immunoglobulin-like receptor, three immunoglobulin domains, and long cytoplasmic tail (KIR3DL3), which is prevalent on terminally differentiated T and CD56dim CD16+ NK cells to transmit inhibitory signals. The expression dynamics of these receptors on immune cells contribute to the maintenance of immune response homeostasis. Therapeutic strategies targeting the HHLA2 immune checkpoint aim to selectively inhibit the immunosuppressive HHLA2-KIR3DL3 pathway while preserving the HHLA2-TMIGD2 signaling. Several anti-HHLA2 and anti-KIR3DL3 antibodies are currently under investigation in early clinical trials, building upon encouraging results observed in humanized mouse models. Notably, the nonoverlapping expression of HHLA2 and PD-L1 in tumors suggests potential synergistic benefits of combining HHLA2-KIR3DL3-targeted therapies with PD-1/PD-L1 blockade or anti-CTLA-4 to augment antitumor activity.</p>","PeriodicalId":16186,"journal":{"name":"Journal of Leukocyte Biology","volume":" ","pages":""},"PeriodicalIF":3.6,"publicationDate":"2025-02-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141554967","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
Fc gamma receptors activate different protein kinase C isoforms in human neutrophils. Fc γ受体可激活人中性粒细胞中不同的蛋白激酶 C 同工酶。
IF 3.6 3区 医学
Journal of Leukocyte Biology Pub Date : 2025-02-13 DOI: 10.1093/jleuko/qiaf019
Omar Rafael Alemán, Carlos Blanco-Camarillo, Nathalia Naranjo-Pinto, Nancy Mora, Carlos Rosales
{"title":"Fc gamma receptors activate different protein kinase C isoforms in human neutrophils.","authors":"Omar Rafael Alemán, Carlos Blanco-Camarillo, Nathalia Naranjo-Pinto, Nancy Mora, Carlos Rosales","doi":"10.1093/jleuko/qiaf019","DOIUrl":"https://doi.org/10.1093/jleuko/qiaf019","url":null,"abstract":"<p><p>Receptors for the Fc portion of IgG antibodies (FcγR) on human neutrophils constitute an important mechanism for recognition of opsonized microorganisms and for cell activation. Human neutrophils express two FcγR: FcγRIIa and FcγRIIIb. Previously, it has been reported that activation of each FcγR induces different neutrophil responses, by triggering distinct signal transduction pathways. Though, what particular signal transduction pathway is triggered by each FcγR has not been completely elucidated. It has also been reported that PKC is important for FcγR signaling, and that each FcγR may activate different PKC isoforms. Therefore, we explored whether FcγRIIa or FcγRIIIb activates different PKC isoforms in human neutrophils, and whether activation of these PKC isoforms results in different neutrophil responses. Hence, either FcγRIIa or FcγRIIIb was selectively cross-linked by monoclonal antibodies in the presence or absence of pharmacological inhibitors for various PKC isoforms. Inhibition of PKCα or PKCδ blocked FcγRIIa-induced reactive oxygen species (ROS) productions. In contrast, inhibition of PKCα and/or PKCβ blocked FcγRIIIb-induced ROS production. Also, inhibition of all PKC isoforms did not affect FcγRIIa-induced increase in intracellular calcium concentration ([Ca2+]i), while inhibition of PKCα blocked FcγRIIIb-induced increase in [Ca2+]i. Additionally, inhibition of PKCδ blocked FcγRIIa-induced ERK phosphorylation, while inhibition of PKCα prevented FcγRIIIb-induced ERK phosphorylation. These results suggest that both FcγRIIa and FcγRIIIb activate unique PKC isoforms, and that activation of these PKC isoforms can selectively regulate different neutrophil functions. These findings also reinforce the idea that each FcγR in human neutrophils triggers distinct signal transduction pathways.</p>","PeriodicalId":16186,"journal":{"name":"Journal of Leukocyte Biology","volume":" ","pages":""},"PeriodicalIF":3.6,"publicationDate":"2025-02-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143414323","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
Development of 2LTRZFP-expressing induced pluripotent stem cells as a potential anti-HIV-1 gene therapy against viral integration. 开发表达 2LTRZFP 的诱导多能干细胞,作为抗 HIV-1 病毒整合的潜在基因疗法。
IF 3.6 3区 医学
Journal of Leukocyte Biology Pub Date : 2025-02-13 DOI: 10.1093/jleuko/qiaf018
Kritayaporn Saiprayong, Koollawat Chupradit, Pasut Sasithong, Siriwal Suwanpitak, Saitong Muneekaew, Nontaphat Thongsin, Jakkrapatra Srisantitham, Methichit Wattanapanitch
{"title":"Development of 2LTRZFP-expressing induced pluripotent stem cells as a potential anti-HIV-1 gene therapy against viral integration.","authors":"Kritayaporn Saiprayong, Koollawat Chupradit, Pasut Sasithong, Siriwal Suwanpitak, Saitong Muneekaew, Nontaphat Thongsin, Jakkrapatra Srisantitham, Methichit Wattanapanitch","doi":"10.1093/jleuko/qiaf018","DOIUrl":"https://doi.org/10.1093/jleuko/qiaf018","url":null,"abstract":"<p><p>Highly active antiretroviral drug (HAART) is the standard treatment for HIV-1 infection to suppress the viral load. However, this treatment does not completely eradicate the virus; it simply decreases the viral load to undetectable levels. The development of a novel therapy to cure the disease is essential. Previously, we developed an engineered zinc finger protein (ZFP) that specifically binds to the 2-LTR-circle junction (2LTRZFP), the target site for viral integrase, preventing HIV-1 integration in human CD34+ hematopoietic stem/progenitor cells (HSPCs) and macrophages. Although the transduction efficiency of 2LTRZFP was approximately 50%, purifying and expanding the 2LTRZFP-expressing HSPCs proved difficult. In addition, the batch-to-batch variability in transduction efficiency could have a major impact on the therapeutic efficacy. In this study, we introduced the 2LTRZFP into human induced pluripotent stem cells (iPSCs) followed by clonal isolation and functional validation of the 2LTRZFP. Upon the HIV-1 challenge, the 2LTRZFP protein was found to inhibit the viral integration in iPSCs, iPSC-derived HSPCs, and macrophages. The engineered iPSC clone could be differentiated into functional macrophages, as evidenced by M1 and M2 polarization, and phagocytosis. Our finding revealed that the 2LTRZFP did not perturb the macrophage differentiation process. Therefore, the 2LTRZFP-expressing iPSCs could provide an unlimited supply of HIV-1-resistant HSPCs for transplantation, potentially leading to HIV-1-resistant blood cells. The knowledge obtained from this study will provide a cornerstone for HIV-1 gene therapy using HSPC transplantation as a sustainable HIV-1 treatment in the future.</p>","PeriodicalId":16186,"journal":{"name":"Journal of Leukocyte Biology","volume":" ","pages":""},"PeriodicalIF":3.6,"publicationDate":"2025-02-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143414335","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
Platycodin D facilitates antiviral immunity through inhibiting cytokine storm via targeting K63-linked TRAF6 ubiquitination. 桔梗皂苷 D 通过靶向 K63 链接的 TRAF6 泛素化抑制细胞因子风暴,从而促进抗病毒免疫。
IF 3.6 3区 医学
Journal of Leukocyte Biology Pub Date : 2025-02-13 DOI: 10.1093/jleuko/qiae075
Hui Liu, Lirong Xu, Enhao Lu, Chenchen Tang, Hanxiao Zhang, Yanwu Xu, Yuanyuan Yu, Naomi Ong, Xiao-Dong Yang, Qilong Chen, Yuejuan Zheng
{"title":"Platycodin D facilitates antiviral immunity through inhibiting cytokine storm via targeting K63-linked TRAF6 ubiquitination.","authors":"Hui Liu, Lirong Xu, Enhao Lu, Chenchen Tang, Hanxiao Zhang, Yanwu Xu, Yuanyuan Yu, Naomi Ong, Xiao-Dong Yang, Qilong Chen, Yuejuan Zheng","doi":"10.1093/jleuko/qiae075","DOIUrl":"10.1093/jleuko/qiae075","url":null,"abstract":"<p><p>Influenza virus infection is a worldwide challenge that causes heavy burdens on public health. The mortality rate of severe influenza patients is often associated with hyperactive immunological abnormalities characterized by hypercytokinemia. Due to the continuous mutations and the occurrence of drug-resistant influenza virus strains, the development of host-directed immunoregulatory drugs is urgently required. Platycodon grandiflorum is among the top 10 herbs of traditional Chinese medicine used to treat pulmonary diseases. As one of the major terpenoid saponins extracted from P. grandiflorum, Platycodin D (PD) has been reported to play several roles, including anti-inflammation, analgesia, anticancer, hepatoprotection, and immunoregulation. However, the therapeutic roles of PD to treat influenza virus infection remain unknown. Here, we show that PD can protect the body weight loss in severely infected influenza mice, alleviate lung damage, and thus improve the survival rate. More specifically, PD protects flu mice via decreasing the immune cell infiltration into lungs and downregulating the overactivated inflammatory response. Western blot and immunofluorescence assays exhibited that PD could inhibit the activation of TAK1/IKK/NF-κB and MAPK pathways. Besides that, cellular thermal shift assay, surface plasmon resonance, and immunoprecipitation assays indicated that PD binds with TRAF6 to decrease its K63 ubiquitination after R837 stimulation. Additionally, small interfering RNA interference experiments exhibited that PD could inhibit the secretion of interleukin-1β and tumor necrosis factor α in TRAF6-dependent manner. Altogether, our results suggested that PD is a promising drug candidate for treating influenza. Our study also offered a scientific explanation for the commonly used P. grandiflorum in many antiepidemic classic formulas. Due to its host-directed regulatory role, PD may serve as an adjuvant therapeutic drug in conjunction with other antiviral drugs to treat the flu.</p>","PeriodicalId":16186,"journal":{"name":"Journal of Leukocyte Biology","volume":" ","pages":""},"PeriodicalIF":3.6,"publicationDate":"2025-02-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140189733","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
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