Journal of Immunology Research最新文献

{"title":"The Research Progress of Tumor-Associated Macrophages in Prostate Cancer.","authors":"Si Shen, Zhonghao Tang, Chen Guo, Anjie Chen, Yuanyuan Mi","doi":"10.1155/jimr/6287638","DOIUrl":"10.1155/jimr/6287638","url":null,"abstract":"<p><p>Prostate cancer (PCa) is a major global cancer burden in men, and its treatment is hindered by the immunosuppressive tumor microenvironment. In this context, PCa initially shows a favorable response to immunotherapy. However, as the disease progresses, the tumor gradually develops resistance to immunotherapy, with tumor-associated macrophages (TAMs) being key drivers. TAMs promote inflammation, angiogenesis, stromal remodeling, and immune evasion, leading to the development of castration-resistant PCa. The traditional M1/M2 dichotomy, such as proliferative-TAM (Prolif-TAM) and immunoregulatory-TAM (Reg-TAM), has been refined by single-cell RNA sequencing. In this article, we further discuss how signaling pathways regulate TAM polarization and investigate the multidimensional mechanisms by which TAMs drive PCa progression, the pathways that promote immunotherapy resistance, and the role of macrophage extracellular traps (METs) in PCa metastasis. Targeting TAMs for precision treatment of PCa is a promising therapeutic strategy. These strategies include blocking the adenosine pathway to inhibit SPP1^hi-TAMs, reprogramming TAMs with immune checkpoint inhibitors (ICIs) to restore chimeric antigen receptor (CAR)-T cell activity, and novel approaches such as using microRNAs (miRNAs) and natural compounds to modulate TAM polarization. However, these treatment modalities still face challenges, including the complexity of the tumor microenvironment (TME) and TAM heterogeneity, obstacles in drug production and delivery, and toxicity management. This article aims to develop individualized targeting strategies based on the composition, functional status, and signaling dependencies of TAM subpopulations within patient tumors, with the hope of transitioning from a \"one-size-fits-all\" approach to precision medicine.</p>","PeriodicalId":15952,"journal":{"name":"Journal of Immunology Research","volume":"2026 1","pages":"e6287638"},"PeriodicalIF":3.2,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13238244/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148163432","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":"Correction to \"Deficiency of IKKα in Macrophages Mitigates Fibrosis Progression in the Kidney after Renal Ischemia-Reperfusion Injury\".","authors":"","doi":"10.1155/jimr/9873896","DOIUrl":"10.1155/jimr/9873896","url":null,"abstract":"","PeriodicalId":15952,"journal":{"name":"Journal of Immunology Research","volume":"2026 1","pages":"e9873896"},"PeriodicalIF":3.2,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13505475/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148813143","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":"Exercise Attenuates Neuroinflammation in Chronic Restraint Stress Induced Depression Model by Downregulating GDF15 Expression.","authors":"Junrui Chen, Chunxiao Du, Jiawen Lu, Meng Liang, Miaonan Sun, Yanmin Lyu, Mengying Huang, Jixiang Sun, Yuxiang Li, Zhiding Wang, Ge Li, Gencheng Han","doi":"10.1155/jimr/6816624","DOIUrl":"10.1155/jimr/6816624","url":null,"abstract":"<p><p>Exercise has been shown to alleviate depressive symptoms and enhance bodily functions. However, the precise mechanisms underlying its antidepressant effects remain incompletely understood. In this study, we observed that treadmill exercise may exert antidepressant effects in a chronic restraint stress (CRS) mouse model by modulating the proinflammatory Growth Differentiation Factor 15 (GDF15)-extracellular signal-regulated kinase (ERK) signaling pathway. Treadmill exercise improved cognitive behaviors in CRS mice and alleviated neuroinflammation, as evidenced by decreased expression of TNF-α, IL-1β, IL-6, and attenuated microglia activation. Intriguingly, we found that treadmill exercise inhibited the expression of GDF15, a biomarker associated with many immune disorders, which is increased following CRS. Mechanistically, treadmill exercise may attenuate neuroinflammation by suppressing GDF15-induced ERK activation. We thus identified a novel mechanism by which treadmill exercise attenuates depression. Modulation of the GDF15-ERK pathway may have therapeutic implications for depression.</p>","PeriodicalId":15952,"journal":{"name":"Journal of Immunology Research","volume":"2026 1","pages":"e6816624"},"PeriodicalIF":3.2,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13581054/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147638899","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":"Spatiotemporal Double-Edged Sword of Macrophages: Temporal Regulation of Neuroinflammation and Neurorepair in Ischemic Stroke.","authors":"Shuwen Zhang, Xinyu Chai, Shanzhu Guo, Yuxi Wang, Yinan Wang, Hongyan Yuan, Dongmei Yan","doi":"10.1155/jimr/1172895","DOIUrl":"10.1155/jimr/1172895","url":null,"abstract":"<p><p>Ischemic stroke (IS) accounts for ~85% of all stroke cases and stands as one of the leading global causes of disability and mortality. Its pathological progression is closely intertwined with intricate inflammatory responses, among which post-stroke activated macrophages are widely recognized as the core drivers and regulators of IS pathogenesis. This review systematically elucidates the dual role of macrophages in stroke: they act as the primary drivers of the acute neuroinflammatory storm, while also serving as key regulators of neurorepair during the subacute and chronic phases. By focusing on the spatiotemporal dynamic changes, polarization regulatory mechanisms, and phenotypic/functional transition patterns of macrophages. This review provides a theoretical foundation for the development of precise therapeutic strategies that target the spatiotemporal dynamics and functional transitions of macrophages.</p>","PeriodicalId":15952,"journal":{"name":"Journal of Immunology Research","volume":"2026 1","pages":"e1172895"},"PeriodicalIF":3.2,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13136591/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147816182","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":"The Role of BMAL1 in Regulating Circadian Rhythms During Airway Remodeling in Asthma.","authors":"Xiaorong Xiang, Caiming Zhong, Hao Tang","doi":"10.1155/jimr/6983721","DOIUrl":"10.1155/jimr/6983721","url":null,"abstract":"<p><p>Asthma is a chronic respiratory disease characterized by airway inflammation, hyperresponsiveness, and remodeling. The circadian clock governs natural 24 h biological rhythms, encompassing physiological, metabolic, and hormonal fluctuations. It regulates key physiological processes like sleep, activity, and feeding, playing a crucial role in maintaining normal respiratory function. However, the mechanisms underlying asthma airway remodeling and its relationship with circadian clock genes remain incompletely understood. Brain and muscle arnt-like 1 (BMAL1), a core circadian clock gene, plays a significant role in the proliferation and differentiation of airway stem cells. This review summarizes recent advances in clinically relevant asthma research, including the role of airway remodeling in disease progression. It then focuses on unresolved scientific questions regarding the function of the BMAL1 gene in asthma pathogenesis, aiming to contribute to the future development of metabolic rhythm-based strategies as novel targets for asthma diagnosis and treatment.</p>","PeriodicalId":15952,"journal":{"name":"Journal of Immunology Research","volume":"2026 1","pages":"e6983721"},"PeriodicalIF":3.2,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13255153/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148217346","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":"CTH Promotes Liver Cancer Progression and Exploratory Evaluation Supports Enhanced Antitumor Activity of PPG Plus GPC3 CAR-T Cells.","authors":"Yuxin Guo, Man Yu, Xilin Zhu, Wei Li, Ying Liu, Xiaopan Wu","doi":"10.1155/jimr/3351382","DOIUrl":"10.1155/jimr/3351382","url":null,"abstract":"<p><p>Although hydrogen sulfide (H₂S) is a key regulator in cancer biology, the mechanism by which the H₂S-producing enzyme cystathionine-γ-lyase (CTH) functions in hepatocellular carcinoma (HCC) remains elusive. Using the slow-releasing H₂S donor GYY4137, we observed enhanced migration and invasion in HuH7 and HepG2 cells. Subsequently, we observed consistent protumorigenic effects of CTH not only in vitro but also in subcutaneous and orthotopic mouse models. Here, our findings suggest that CTH-H₂S sulfhydrates Rab7a, which may be associated with HCC progression. We further showed that CTH modulates the expression of autophagy-related proteins in liver tumor cells. In nude mouse subcutaneous xenograft experiments, compared with the vehicle group, the combination of DL-propargylglycine (PPG, CTH inhibitor) and GPC3 CAR-T exhibited better antitumor efficacy compared to PPG or CAR-T alone. Our findings suggest that CTH modulation was associated with altered Rab7a sulfhydration and autophagy and that combined PPG and GPC3 CAR-T therapy exerts better antitumor efficacy.</p>","PeriodicalId":15952,"journal":{"name":"Journal of Immunology Research","volume":"2026 1","pages":"e3351382"},"PeriodicalIF":3.2,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13673299/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149194632","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":"Structural and Functional Alterations of MAMs and Their Immunomodulatory Roles in Sepsis-Induced Lung Injury.","authors":"Yihao Wang, Jingran Yang, Xia Li","doi":"10.1155/jimr/9888339","DOIUrl":"10.1155/jimr/9888339","url":null,"abstract":"<p><strong>Background: </strong>Sepsis-induced acute lung injury (SI-ALI) is a major cause of morbidity and mortality among septic patients. Recent evidence highlights the role of mitochondria-associated membranes (MAMs)-specialized contact sites between the endoplasmic reticulum (ER) and mitochondria-in regulating calcium signaling, lipid metabolism, energy homeostasis, and immune responses. Structural and functional alterations of MAMs are increasingly recognized as critical contributors to the pathogenesis of SI-ALI.</p><p><strong>Objectives: </strong>This review aims to summarize the structural and functional characteristics of MAMs, elucidate their alterations and immunoregulatory roles in sepsis-induced lung injury, and discuss potential therapeutic strategies targeting MAMs to mitigate pulmonary damage.</p><p><strong>Methods: </strong>A comprehensive literature review was conducted using recent studies focused on the molecular structure, signaling mechanisms, and pathological changes of MAMs in sepsis and related inflammatory diseases. Emphasis was placed on calcium signaling, mitochondrial dysfunction, oxidative stress, and inflammasome activation.</p><p><strong>Results: </strong>MAMs maintain close ER-mitochondria contacts (10-30 nm) through key proteins such as inositol 1,4,5-trisphosphate receptor (IP3R), glucose-regulated protein 75 (GRP75), voltage-dependent anion channel (VDAC), and mitofusin-2 (MFN2). During sepsis, oxidative stress and inflammatory cytokines disrupt these contacts, leading to impaired calcium transfer, mitochondrial dysfunction, and energy deficiency. Dysregulated MAMs promote NLR family pyrin domain containing 3 (NLRP3) inflammasome activation, excessive reactive oxygen species (ROS) production, and mitochondrial DNA (mtDNA) release, thereby amplifying inflammatory cascades and immune cell apoptosis. Therapeutic strategies that restore MAM integrity-such as upregulating MFN2, activating ER autophagy, or modulating calcium transport proteins-have shown potential to attenuate lung injury by improving mitochondrial metabolism and reducing oxidative stress.</p><p><strong>Conclusions: </strong>MAMs play essential roles in maintaining intracellular homeostasis and immune balance. Their structural and functional disruption contributes significantly to the progression of SI-ALI. Targeting MAMs offers promising therapeutic opportunities for preventing and treating sepsis-induced lung injury, although further mechanistic and clinical studies are warranted to translate these findings into practice.</p>","PeriodicalId":15952,"journal":{"name":"Journal of Immunology Research","volume":"2026 1","pages":"e9888339"},"PeriodicalIF":3.2,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13130853/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147773370","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":"Phosphatidylserine Blockade Limits Systemic Dissemination of Leishmania Amazonensis Amastigotes.","authors":"Arieli Bernardo Portugal, Suzana Passos Chaves, Renato Augusto DaMatta, João Luiz Mendes Wanderley","doi":"10.1155/jimr/4561938","DOIUrl":"10.1155/jimr/4561938","url":null,"abstract":"<p><p>Leishmania amazonensis is associated with cases of cutaneous, disseminated, diffuse, mucosal, and visceral leishmaniasis (VL). The mechanisms underlying its ability to persist and spread after the initial clinical cure are unclear, although intrinsic characteristics of the parasite and the host may be involved. Phosphatidylserine (PS) is a pathogenic factor in both experimental models and in patients. It is related to macrophage infection, regulation of inflammatory and immune responses, and the extent and severity of the clinical outcomes of the disease. In a murine model of systemic infection, treatment with PS-targeting antagonist antibodies significantly reduced parasite burden in the spleen. In parallel, the number and size of disseminated skin lesions were consistently reduced. These effects correlated with a substantial decrease in interleukin-10 (IL-10) and transforming growth factor-β (TGF-β) production by splenocytes stimulated with leishmanial antigens, indicating a reversal of the regulatory immune profile commonly associated with chronic infection. These findings support a critical role for PS in the dissemination and visceralization of Leishmania amazonensis, highlighting its contribution to immune evasion and the pathogenesis of severe disease forms.</p>","PeriodicalId":15952,"journal":{"name":"Journal of Immunology Research","volume":"2026 1","pages":"e4561938"},"PeriodicalIF":3.2,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13679095/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149220488","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":"RETRACTION: Circular RNA RHOT1 Regulates miR-142-5p/CCND1 to Participate in Chondrocyte Autophagy and Proliferation in Osteoarthritis.","authors":"Journal Of Immunology Research","doi":"10.1155/jimr/9874925","DOIUrl":"10.1155/jimr/9874925","url":null,"abstract":"","PeriodicalId":15952,"journal":{"name":"Journal of Immunology Research","volume":"2026 1","pages":"e9874925"},"PeriodicalIF":3.6,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13140865/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147433336","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":"Tissue-Specific Expansion of Age-Associated B Cells via IFN-γ and IL-21 Within Salivary Glands in Sjögren Disease.","authors":"Mari Nishida, Kunihiro Otsuka, Ruka Nagao, Shigefumi Matsuzawa, Aya Ushio, Takaaki Tsunematsu, Keiko Aota, Naozumi Ishimaru","doi":"10.1155/jimr/4221251","DOIUrl":"10.1155/jimr/4221251","url":null,"abstract":"<p><p>Sjögren disease (SjD) is an autoimmune disorder that predominantly affects the exocrine glands, and advancing age is recognized as an important risk factor for its development. However, the mechanisms linking age and disease progression remain poorly understood. Age-associated B cells (ABCs), a subset of B cells that increase with age, have been implicated in autoimmune responses, but their role in SjD pathogenesis has not been fully clarified. In this study, we examined labial salivary glands (LSGs) from 44 SjD patients and 11 non-SjD sicca controls. T-bet⁺ CD20⁺ ABCs were detected infiltrating the glands in SjD patients, especially in individuals in their 40s-60s, but were rare in non-SjD sicca controls. To investigate the underlying mechanisms, we used a SjD mouse model at various ages. ABCs (CD11b⁺ CD95⁺ CD19⁺) began locally accumulating in the SGs from the mature-adult stage, earlier than in age-matched controls, while remaining low in cervical lymph nodes (cLNs). To explore the drivers of ABC expansion, we examined the factors involved in ABC differentiation, focusing on interleukin-21 (IL-21) and interferon-gamma (IFN-γ). This combination of IL-21 and IFN-γ upregulated T-bet expression on B cells in SjD model mice. In situ hybridization (ISH) and flow cytometric analysis revealed that CD4⁺ T cells, especially follicular helper T (Tfh)-like cells were a major source of IL-21 in the SGs of mature-adult-SjD mice. Additionally, ABCs themselves showed elevated expression of IFN-γ compared to other immune cells, indicating an autocrine mechanism promoting their expansion. Our findings suggest that ABCs accumulate in the SGs of SjD patients and model mice through IL-21 signaling from CD4⁺ T cells and autocrine IFN-γ activity. This localized expansion may contribute to autoimmune tissue damage. These results provide new insights into how aging-associated immune changes may drive the development and progression of SjD, offering potential targets for therapeutic intervention.</p>","PeriodicalId":15952,"journal":{"name":"Journal of Immunology Research","volume":"2026 1","pages":"e4221251"},"PeriodicalIF":3.2,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13140891/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147504196","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}