Immune Network最新文献

Soluble CCR2-Expressing Mesenchymal Stem Cells Inhibit Osteoarthritis Development and Progression. 可溶性表达ccr2的间充质干细胞抑制骨关节炎的发生和进展

IF 4.3 4区医学

Immune Network Pub Date : 2025-06-16 eCollection Date: 2025-06-01 DOI: 10.4110/in.2025.25.e24

Hyun Sik Na, Seon-Young Lee, Dong Hwan Lee, Keun-Hyung Cho, Seon Ae Kim, Eun Jeong Go, A Ram Lee, Jeong Su Lee, Yeon Su Lee, In Gyu Um, Se Gyeong Han, Mi-La Cho, Seok Jung Kim

{"title":"Soluble CCR2-Expressing Mesenchymal Stem Cells Inhibit Osteoarthritis Development and Progression.","authors":"Hyun Sik Na, Seon-Young Lee, Dong Hwan Lee, Keun-Hyung Cho, Seon Ae Kim, Eun Jeong Go, A Ram Lee, Jeong Su Lee, Yeon Su Lee, In Gyu Um, Se Gyeong Han, Mi-La Cho, Seok Jung Kim","doi":"10.4110/in.2025.25.e24","DOIUrl":"10.4110/in.2025.25.e24","url":null,"abstract":"Many studies of osteoarthritis (OA) have focused on the use of pain-suppressing drugs and stem cell treatments for cartilage repair. In a previous study, we reported the therapeutic effect of soluble C-C chemokine receptor type 2 (sCCR2) gene therapy on OA. Here, we aimed to demonstrate that sCCR2-expressing stem cells exhibits superior efficacy compared to mesenchymal stem cell (MSC) alone. We used monosodium iodoacetate to induce OA in a Wistar rat model for our experiments. Soluble form of CCR2 was transfected into chondrocytes. We analyzed both in vitro and in vivo systems using sCCR2 E3-transfected MSCs (sCEMs). MCP-1 reduced chondrogenesis, whereas sCEMs improved it. Additionally, disease development was suppressed in MCP-1 conditional knockout mice. In the OA rat model, injection of sCEMs showed significant effects with respect to pain control and reduction of joint cartilage inflammation and damage compared with injection of MOCK-MSCs. These findings indicate that sCEMs inhibit MCP-1, reducing pain and OA-induced cartilage damage and inducing chondroprotection. Inhibiting MCP-1/CCR2 signaling has a significant therapeutic effect on OA. Therefore, sCEM may be an effective treatment for OA.","PeriodicalId":13307,"journal":{"name":"Immune Network","volume":"25 3","pages":"e24"},"PeriodicalIF":4.3,"publicationDate":"2025-06-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12226253/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144575394","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Nanobody-Based CAR NK Cells for Possible Immunotherapy of Mesothelin⁺ Tumors. 纳米体CAR - NK细胞可能用于间皮素+肿瘤的免疫治疗。

IF 4.3 4区医学

Immune Network Pub Date : 2025-06-13 eCollection Date: 2025-06-01 DOI: 10.4110/in.2025.25.e23

Dana Jung, Eunjeong Choi, Young-Hee Jeoung, Juheon Lee, Eun-Yeung Gong, Seo-Gyeong Jo, Kyunghee Noh, Kyungsoo Ha, Gabbine Wee, Hyeran Kim, Juyeon Jung, Seokho Kim

{"title":"Nanobody-Based CAR NK Cells for Possible Immunotherapy of Mesothelin+ Tumors.","authors":"Dana Jung, Eunjeong Choi, Young-Hee Jeoung, Juheon Lee, Eun-Yeung Gong, Seo-Gyeong Jo, Kyunghee Noh, Kyungsoo Ha, Gabbine Wee, Hyeran Kim, Juyeon Jung, Seokho Kim","doi":"10.4110/in.2025.25.e23","DOIUrl":"10.4110/in.2025.25.e23","url":null,"abstract":"Chimeric Ag receptor (CAR)-engineered immune cells have demonstrated remarkable clinical efficacy, particularly in hematologic malignancies. Central to their success is the Ag-binding domain of the CAR, which governs both target specificity and therapeutic efficacy. Nanobodies (Nbs) possess a single-domain architecture and smaller molecular size, making them particularly amenable to the construction of tandem CARs that can co-target multiple Ags. This structural flexibility is advantageous for addressing tumor heterogeneity and reducing the risk of Ag escape in solid malignancies. Here, we developed mesothelin (MSLN)-specific nanobody-based chimeric Ag receptor-NK (Nb CAR-NK) cells using a synthetic nanobody identified from a phage display VHH library. The nanobody was selected after three rounds of biopanning and validated for high affinity and specificity using surface plasmon resonance and flow cytometry. The selected nanobody-based chimeric Ag receptor (Nb-CAR) construct was introduced into ex vivo expanded umbilical cord blood-derived NK cells via third-generation lentiviral transduction, resulting in stable expression and functional CAR-NK cells. The Nb CAR-NK cells exhibited potent cytotoxicity against MSLN-positive pancreatic cancer cells in vitro and significantly suppressed tumor growth in xenograft models. These findings support the clinical potential of Nb CAR-NK cells and highlight the value of Nb-CAR designs for targeting cell-surface Ags in solid tumors.","PeriodicalId":13307,"journal":{"name":"Immune Network","volume":"25 3","pages":"e23"},"PeriodicalIF":4.3,"publicationDate":"2025-06-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12226252/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144575392","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

The Diverse Function of IL-6 in Biological Processes and the Advancement of Cancer. IL-6在生物过程和癌症进展中的多种功能。

IF 4.3 4区医学

Immune Network Pub Date : 2025-06-11 eCollection Date: 2025-06-01 DOI: 10.4110/in.2025.25.e22

Ying Zhou, Xiaofeng Song, Miaomiao Yuan, Yongli Li

引用次数: 0

Ubiquitin-like Proteins in Autoimmune Diseases: Current Evidence and Therapeutic Opportunities. 自身免疫性疾病中的泛素样蛋白：目前的证据和治疗机会。

IF 4.3 4区医学

Immune Network Pub Date : 2025-05-01 eCollection Date: 2025-06-01 DOI: 10.4110/in.2025.25.e21

Beomgu Lee, Hoim Jeong, Yerin Kim, Jong Seong Roh, Dong Hyun Sohn

{"title":"Ubiquitin-like Proteins in Autoimmune Diseases: Current Evidence and Therapeutic Opportunities.","authors":"Beomgu Lee, Hoim Jeong, Yerin Kim, Jong Seong Roh, Dong Hyun Sohn","doi":"10.4110/in.2025.25.e21","DOIUrl":"10.4110/in.2025.25.e21","url":null,"abstract":"Autoimmune diseases encompass a diverse group of disorders characterized by misdirected immune responses against own tissues and organs. In recent decades, the prevalence of autoimmune diseases has steadily increased. Although anti-inflammatory treatments are highly effective for autoimmune diseases, they also cause immunosuppression, leading to an increased risk of cancers and opportunistic infections. Moreover, current treatments primarily focus on suppressing inflammation rather than addressing the underlying causes. Therefore, a comprehensive understanding of the molecular and cellular events within the affected cells is crucial for the development of treatments. Ubiquitin plays a critical role in maintaining cellular homeostasis through processes such as target protein degradation, protein trafficking, and receptor-mediated endocytosis through the E1-E2-E3 cascade. In addition, several ubiquitin-like proteins (UBLs), which share structural similarities with ubiquitin, participate in E1-E2-E3 cascade-mediated processes, thereby expanding the regulatory landscape. Among these UBLs, small ubiquitin-like modifier, interferon-stimulated gene 15, neural precursor cell expressed developmentally down-regulated protein 8, and human leukocyte antigen-F adjacent transcript 10 play distinct roles in the immune system. This review highlights the roles of UBLs in the development of autoimmune diseases. Understanding these functions provides novel insights into molecular mechanisms underlying the development of autoimmune diseases.","PeriodicalId":13307,"journal":{"name":"Immune Network","volume":"25 3","pages":"e21"},"PeriodicalIF":4.3,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12226256/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144575398","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Strong Immune Privileges of MSC and Other Nes-GFP⁺ Progenitors in Bone Marrow of Transgenic Mice. MSC和其他Nes-GFP+祖细胞在转基因小鼠骨髓中的强免疫特权

IF 4.3 4区医学

Immune Network Pub Date : 2025-04-22 eCollection Date: 2025-06-01 DOI: 10.4110/in.2025.25.e20

Dmitriy Karpenko, Nikolay Kapranov, Aleksei Bigildeev

引用次数: 0

SiglecF Expressing Neutrophils Exacerbate Th17-Mediated Autoimmune Neuroinflammation. 表达中性粒细胞SiglecF加剧th17介导的自身免疫性神经炎症。

IF 4.3 4区医学

Immune Network Pub Date : 2025-04-14 eCollection Date: 2025-06-01 DOI: 10.4110/in.2025.25.e19

Wonseok Hu, Leezhi Kwon, Yu Sun Jeong, Geon Ho Bae, Ye Seon Kim, Brian A Zabel, Yoe-Sik Bae

{"title":"SiglecF Expressing Neutrophils Exacerbate Th17-Mediated Autoimmune Neuroinflammation.","authors":"Wonseok Hu, Leezhi Kwon, Yu Sun Jeong, Geon Ho Bae, Ye Seon Kim, Brian A Zabel, Yoe-Sik Bae","doi":"10.4110/in.2025.25.e19","DOIUrl":"10.4110/in.2025.25.e19","url":null,"abstract":"Multiple sclerosis is an autoimmune disease characterized by numerous immune cells, including neutrophils, infiltrating the central nervous system. Previous reports point to a complex role for neutrophils in experimental autoimmune encephalomyelitis (EAE), where their heterogeneity remains poorly understood. In this study, we identified a unique population of neutrophils expressing SiglecF in the brain during EAE that can influence T cell activity. These neutrophils produced elevated levels of Th17-polarizing cytokines, including IL-6, IL-1β, IL-23, and TNF-α, both in vivo and in vitro. Consistent with this cytokine profile, co-culturing SiglecF+ neutrophils with CD4+ T cells promoted Th17 and GM-CSF+ pathogenic Th17 differentiation and proliferation while reducing regulatory T cell numbers. Depleting SiglecF+ neutrophils with anti-SiglecF Abs reduced the severity of EAE, decreased the Th17 population, and increased the regulatory T cell population in the brain. These findings suggest that SiglecF+ neutrophils promote autoimmune neuroinflammation by reinforcing pathogenic autoreactive Th17 cell responses.","PeriodicalId":13307,"journal":{"name":"Immune Network","volume":"25 3","pages":"e19"},"PeriodicalIF":4.3,"publicationDate":"2025-04-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12226254/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144575393","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Cytokines in Focus: IL-2 and IL-15 in NK Adoptive Cell Cancer Immunotherapy. 细胞因子的焦点：IL-2和IL-15在NK过继细胞癌免疫治疗中的作用。

IF 4.3 4区医学

Immune Network Pub Date : 2025-04-09 eCollection Date: 2025-04-01 DOI: 10.4110/in.2025.25.e17

Bryan Marr, Donghyeon Jo, Mihue Jang, Seung-Hwan Lee

引用次数: 0

Novel STAT3 Y360C Gain-of-function Variant Underlies Immune Dysregulation and Aberrancy in Mitochondrial Dynamics. 新的STAT3 Y360C功能获得变异是线粒体动力学免疫失调和异常的基础。

IF 4.3 4区医学

Immune Network Pub Date : 2025-04-09 eCollection Date: 2025-04-01 DOI: 10.4110/in.2025.25.e18

Kornvalee Meesilpavikkai, Kasiphak Kaikaew, Zijun Zhou, Virgil A S H Dalm, Fabian M P Kaiser, Christopher Schliehe, Sigrid M A Swagemakers, Peter J van der Spek, Benjamin Schrijver, Pamela Vasic, Maaike de Bie, Marleen Bakker, Chiara Milanese, Pier G Mastroberardino, Nattiya Hirankarn, Narissara Suratannon, Hanna IJspeert, Willem A Dik, P Martin van Hagen

{"title":"Novel STAT3 Y360C Gain-of-function Variant Underlies Immune Dysregulation and Aberrancy in Mitochondrial Dynamics.","authors":"Kornvalee Meesilpavikkai, Kasiphak Kaikaew, Zijun Zhou, Virgil A S H Dalm, Fabian M P Kaiser, Christopher Schliehe, Sigrid M A Swagemakers, Peter J van der Spek, Benjamin Schrijver, Pamela Vasic, Maaike de Bie, Marleen Bakker, Chiara Milanese, Pier G Mastroberardino, Nattiya Hirankarn, Narissara Suratannon, Hanna IJspeert, Willem A Dik, P Martin van Hagen","doi":"10.4110/in.2025.25.e18","DOIUrl":"https://doi.org/10.4110/in.2025.25.e18","url":null,"abstract":"The STAT3 is an important regulator in a wide range of different cell types. Human STAT3 variants are associated with several immune dysregulation diseases. The current study investigated the clinical, genetic, and immunobiological data obtained from a family with novel heterozygous STAT3 variants located at p.Y360C of the DNA binding domain. The clinical manifestations of these patients include autoimmunity, immunodeficiency, and postnatal growth defects. Broad STAT3 regulated cells including patient primary immune cells and HEK293 cells harboring the variant were assessed. Remarkably high levels of STAT3-regulated cytokines were detected in the sera of the patients. STAT3 nuclear binding and STAT3 activity were higher in STAT3-transduced HEK293 cells containing the p.Y360C variant when compared to HEK cells expressing wild type (WT) STAT3. Upon cytokine activation, STAT3 variants inhibited nuclear translocation of the WT STAT3 molecule. We also demonstrated that PBMCs from these patients exhibit significantly higher mitochondrial activity compared to that of healthy controls. The exploration of the effects of STAT3 Y360C variants described in our study provides novel insights into the molecular effects of the STAT3 variant and its role in the pathophysiology of STAT3 gain-of-function syndromes.","PeriodicalId":13307,"journal":{"name":"Immune Network","volume":"25 2","pages":"e18"},"PeriodicalIF":4.3,"publicationDate":"2025-04-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12056293/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144010707","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Succinate Dehydrogenase Regulates Homeostasis and Metabolic Integrity of Alveolar Macrophages. 琥珀酸脱氢酶调节肺泡巨噬细胞的稳态和代谢完整性。

IF 4.3 4区医学

Immune Network Pub Date : 2025-04-08 eCollection Date: 2025-06-01 DOI: 10.4110/in.2025.25.e16

Seung Geun Song, Ein Lee, Jaemoon Koh, Doo Hyun Chung

{"title":"Succinate Dehydrogenase Regulates Homeostasis and Metabolic Integrity of Alveolar Macrophages.","authors":"Seung Geun Song, Ein Lee, Jaemoon Koh, Doo Hyun Chung","doi":"10.4110/in.2025.25.e16","DOIUrl":"10.4110/in.2025.25.e16","url":null,"abstract":"Lung tissue-resident macrophages, including alveolar macrophages (AMs) and interstitial macrophages (IMs), are pivotal in maintaining both immune defense and tissue homeostasis. Although the distinct functional roles of these macrophage populations are well recognized, the specific metabolic pathways that support their functions are not fully understood. Comparative RNA sequencing analysis identified Sdha, a key enzyme in mitochondrial metabolism, as one of the most highly expressed and differentially regulated genes involved in metabolic pathways in AMs relative to IMs. This finding led us to investigate the role of succinate dehydrogenase complex subunit A (SDHA) in regulating AM metabolism and function. Here, we demonstrated that SDHA is crucial for maintaining AM homeostasis. Deletion of SDHA resulted in a significant reduction in AM populations without affecting IMs, highlighting an AM-specific requirement for SDHA. In the absence of SDHA, AMs underwent metabolic reprogramming towards glycolysis compared with IMs, along with significant transcriptional changes and cell death. Furthermore, SDHA-deficient AMs showed lipid accumulation and increased endoplasmic reticulum stress. These findings establish SDHA as a crucial regulator of AM metabolism and underscore the importance of maintaining metabolic integrity for AM function and survival within the lung microenvironment.","PeriodicalId":13307,"journal":{"name":"Immune Network","volume":"25 3","pages":"e16"},"PeriodicalIF":4.3,"publicationDate":"2025-04-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12226257/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144575396","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Regulatory T Cell Metabolism: A Promising Therapeutic Target for Cancer Treatment? 调节性T细胞代谢：一个有希望的癌症治疗靶点？

IF 4.3 4区医学

Immune Network Pub Date : 2025-02-24 eCollection Date: 2025-02-01 DOI: 10.4110/in.2025.25.e13

Jihyoun Kim, Jiaoran Li, Jun Wei, Seon Ah Lim

{"title":"Regulatory T Cell Metabolism: A Promising Therapeutic Target for Cancer Treatment?","authors":"Jihyoun Kim, Jiaoran Li, Jun Wei, Seon Ah Lim","doi":"10.4110/in.2025.25.e13","DOIUrl":"10.4110/in.2025.25.e13","url":null,"abstract":"Regulatory T (Treg) cells are essential for maintaining immune homeostasis by suppressing excessive immune responses. In the context of cancer, however, Tregs promote immune evasion and tumor progression, particularly through their unique adaptations within the tumor microenvironment (TME). Recent research has emphasized how metabolic characteristics shape Treg activation, migration, and immunosuppressive function, revealing the impact of metabolic pathways on Treg fitness in homeostasis and within the TME. In this review, we first provide an overview of Tregs in cancer immunology, discussing their immunosuppressive roles and properties specific to the TME. We then examine the metabolic requirements for Treg activation and migration under normal conditions, followed by a discussion of how hypoxia, lactate accumulation, nutrient limitation, oxidative stress, and other TME-specific factors alter Treg metabolism and contribute to cancer immune evasion. Finally, we explore therapeutic strategies that target Treg metabolism within the TME, including pharmacological modulation of specific metabolic pathways to diminish Treg-mediated immunosuppression. Thus, we could suggest future directions and clinical implications for Treg-targeted metabolic modulation as a complementary approach in cancer treatment, setting the stage for novel strategies in immunotherapy.","PeriodicalId":13307,"journal":{"name":"Immune Network","volume":"25 1","pages":"e13"},"PeriodicalIF":4.3,"publicationDate":"2025-02-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11896657/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143614803","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0