Journal of Leukocyte Biology最新文献

{"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}

{"title":"Interferon-gamma induces epithelial reprogramming driving CXCL11-mediated T-cell migration.","authors":"Alessandro Cutilli, Suze A Jansen, Francesca Paolucci, Marliek van Hoesel, Cynthia L Frederiks, Tessa A M Mulder, Theofilos Chalkiadakis, Michal Mokry, Stefan Prekovic, Enric Mocholi, Caroline A Lindemans, Paul J Coffer","doi":"10.1093/jleuko/qiae205","DOIUrl":"10.1093/jleuko/qiae205","url":null,"abstract":"<p><p>The cytokine interferon-gamma plays a multifaceted role in intestinal immune responses ranging from anti- to proinflammatory depending on the setting. Here, using a 3D co-culture system based on human intestinal epithelial organoids, we explore the capacity of interferon-gamma exposure to reprogram intestinal epithelia and thereby directly modulate lymphocyte responses. Interferon-gamma treatment of organoids led to transcriptional reprogramming, marked by a switch to a proinflammatory gene expression profile, including transcriptional upregulation of the chemokines CXCL9, CXCL10, and CXCL11. Proteomic analysis of organoid-conditioned medium posttreatment confirmed chemokine secretion. Interferon-gamma treatment of organoids led to enhanced T-cell migration in a CXCL11-dependent manner without affecting T-cell activation status. Taken together, our results suggest a specific role for CXCL11 in T-cell recruitment that could be targeted to prevent T-cell trafficking to the inflamed intestine.</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":"142289242","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}

{"title":"Thymic stromal lymphopoietin signaling in B cells from progenitors to plasma cells.","authors":"Phillip P Domeier, Steven F Ziegler","doi":"10.1093/jleuko/qiae216","DOIUrl":"10.1093/jleuko/qiae216","url":null,"abstract":"<p><p>Thymic stromal lymphopoietin is an established pleotropic alarmin cytokine that is generated at barrier tissues to induce type 2 immune responses, but its role in regulating the diversity of B cells is poorly understood. Here, we will highlight the key findings that underpin our limited understanding of the role thymic stromal lymphopoietin in modulating different stages of B cell development. We will also provide an overview of how thymic stromal lymphopoietin drives B cell-mediated immune disease and how novel thymic stromal lymphopoietin-blocking biologics could be used to modulate B cell responses. Thymic stromal lymphopoietin is critical for the regulation, diversity, and longevity of humoral immunity.</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":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11878999/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142381017","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"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}

{"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}

{"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}

{"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}

{"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}

{"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}

{"title":"Development of glypican-3-specific chimeric antigen receptor-modified natural killer cells and optimization as a therapy for hepatocellular carcinoma.","authors":"Bihui Cao, Qianqian Ni, Zhuxin Chen, Shuo Yang, Xinkui Zhang, Haotao Su, Zhenfeng Zhang, Qi Zhao, Xiaolan Zhu, Manting Liu","doi":"10.1093/jleuko/qiae144","DOIUrl":"10.1093/jleuko/qiae144","url":null,"abstract":"<p><p>Hepatocellular carcinoma (HCC) is a highly malignant tumor characterized by insidious onset and rapid progression, with limited treatment choices. One treatment modality, chimeric antigen receptor (CAR)-modified natural killer (NK) cell immunotherapy, has shown promise for various cancers. However, the treatment efficacy of CAR-NK cells for HCC remain inferior. In this study, we developed two glypican-3 (GPC3)-specific CAR-NK-92 cell lines (GPC3-CAR-NK) and explored their antitumor efficacy for the treatment of HCC. Significant levels of cytokine production and in vitro cytotoxicity were produced following co-culture of GPC3+ HCC cells with the developed GPC3-CAR-NK cells. GC33-G2D-NK cells with NK cell-specific signaling domains showed better activation and killing abilities than GC33-CD28-NK cells containing T-cell-specific signaling domains. Moreover, GC33-G2D-NK cells efficiently eliminated tumors in cell-derived xenograft and patient-derived xenograft mouse models. In an abdominal metastasis model, intraperitoneally delivered GC33-G2D-NK cells showed better antitumor ability than intravenously injected cells. Finally, the combination of microwave ablation (MWA) with GC33-G2D-NK cell administration showed greater CAR-NK infiltration and tumor regression in ablated tumors than monotherapy alone. These findings indicate that administration of GPC3-CAR-NK cells may be a potential strategy for the treatment of HCC, and regional delivery or their combination with MWA may optimize their efficacy against HCC and may have translational value.</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":"141450690","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}