Immune NetworkPub Date : 2025-02-24eCollection Date: 2025-02-01DOI: 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":"<p><p>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.</p>","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}
Immune NetworkPub Date : 2025-02-24eCollection Date: 2025-02-01DOI: 10.4110/in.2025.25.e15
Sung-Gyoo Park, June-Yong Lee, Hyungseok Seo, Soo Seok Hwang, Chong-Kil Lee, Gap Ryol Lee
{"title":"Modulation of Immune Responses by Metabolic Reprogramming: The Key Role of Immunometabolism.","authors":"Sung-Gyoo Park, June-Yong Lee, Hyungseok Seo, Soo Seok Hwang, Chong-Kil Lee, Gap Ryol Lee","doi":"10.4110/in.2025.25.e15","DOIUrl":"10.4110/in.2025.25.e15","url":null,"abstract":"","PeriodicalId":13307,"journal":{"name":"Immune Network","volume":"25 1","pages":"e15"},"PeriodicalIF":4.3,"publicationDate":"2025-02-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11896660/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143614834","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}
Immune NetworkPub Date : 2025-02-24eCollection Date: 2025-02-01DOI: 10.4110/in.2025.25.e14
Minju Choi, Sujin Choi, Minkyeong Cho, Chulwoo Kim
{"title":"Metabolic Signaling as a Driver of T Cell Aging.","authors":"Minju Choi, Sujin Choi, Minkyeong Cho, Chulwoo Kim","doi":"10.4110/in.2025.25.e14","DOIUrl":"10.4110/in.2025.25.e14","url":null,"abstract":"<p><p>Aging significantly diminishes T cell immunity, increasing susceptibility to infections and reducing vaccine efficacy in older individuals. Metabolism plays a key role in T cell function, shaping their energy requirements, activation, and differentiation. Recent studies highlight altered metabolic signaling as a pivotal factor in T cell aging, influencing the ability of T cells to maintain quiescence, respond to activation, and differentiate into functional subsets. Aberrant metabolic pathways disrupt the quiescence of aged T cells and skew their differentiation toward short-lived, pro-inflammatory effector T cells while hindering the generation of long-lived memory and T follicular helper cells. These changes contribute to a hyper-inflammatory state, exacerbate chronic low-grade inflammation, and compromise immune homeostasis. In this review, we explore how metabolic signaling is altered during T cell aging and the resulting functional impacts. We also discuss therapeutic approaches aimed at restoring proper T cell differentiation, improving vaccine responses, and rejuvenating immune function in older populations.</p>","PeriodicalId":13307,"journal":{"name":"Immune Network","volume":"25 1","pages":"e14"},"PeriodicalIF":4.3,"publicationDate":"2025-02-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11896665/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143614831","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}
Immune NetworkPub Date : 2025-02-21eCollection Date: 2025-02-01DOI: 10.4110/in.2025.25.e12
Jun Hee Jang, Jin Hyun Sung, Jin Young Huh
{"title":"Diverse Functions of Macrophages in Obesity and Metabolic Dysfunction-Associated Steatotic Liver Disease: Bridging Inflammation and Metabolism.","authors":"Jun Hee Jang, Jin Hyun Sung, Jin Young Huh","doi":"10.4110/in.2025.25.e12","DOIUrl":"10.4110/in.2025.25.e12","url":null,"abstract":"<p><p>Macrophages play crucial roles in immune response and tissue homeostasis, with their functions becoming increasingly complex in obesity-mediated metabolic disorders. This review explores the extensive range of macrophage activities within adipose and liver tissues, emphasizing their contribution to the pathogenesis and progression of obesity and its related metabolic dysfunction-associated steatotic liver disease (MASLD). In the context of obesity, macrophages respond adaptively to lipid overloads and inflammatory cues in adipose tissue, profoundly influencing insulin resistance and metabolic homeostasis. Concurrently, their role in the liver extends to moderating inflammation and orchestrating fibrotic responses, integral to the development of MASLD. Highlighting the spectrum of macrophage phenotypes across these metabolic landscapes, we summarize their diverse roles in linking inflammatory processes with metabolic functions. This review advocates for a deeper understanding of macrophage subsets in metabolic tissues, proposing targeted research to harness their therapeutic potential in mitigating MASLD and other metabolic disorders.</p>","PeriodicalId":13307,"journal":{"name":"Immune Network","volume":"25 1","pages":"e12"},"PeriodicalIF":4.3,"publicationDate":"2025-02-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11896663/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143614827","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}
Immune NetworkPub Date : 2025-02-18eCollection Date: 2025-02-01DOI: 10.4110/in.2025.25.e11
Jonathan R Mattingly, Aimee Wu, Autumn G York
{"title":"Regulation of Adaptive Immunity by Lipid Post-translational Modifications.","authors":"Jonathan R Mattingly, Aimee Wu, Autumn G York","doi":"10.4110/in.2025.25.e11","DOIUrl":"10.4110/in.2025.25.e11","url":null,"abstract":"<p><p>The burgeoning field of immunometabolism highlights the interdependence between metabolic programs and efficacious immune responses. The current understanding that cellular metabolic remodeling is necessary for a competent adaptive immune response, along with acutely sensitive methodologies such as high-performance liquid chromatography/mass spectrometry and advanced proteomics, have ushered in a renaissance of lipid- and metabolic-based scientific inquiries. One facet of recent interest examines how lipids function as post-translational modifications (PTMs) and their resulting effects on adaptive immune responses. The goal of this review is to establish a fundamental understanding of these protein modifications and highlight recent findings that underscore the importance of continued investigation into lipids as PTMs.</p>","PeriodicalId":13307,"journal":{"name":"Immune Network","volume":"25 1","pages":"e11"},"PeriodicalIF":4.3,"publicationDate":"2025-02-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11896658/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143614836","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}
{"title":"Mitochondrial Regulator CRIF1 Plays a Critical Role in the Development and Homeostasis of Alveolar Macrophages via Maintaining Metabolic Fitness.","authors":"Ein Lee, Seung Geun Song, Haaun Moon, Minho Shong, Doo Hyun Chung","doi":"10.4110/in.2025.25.e9","DOIUrl":"10.4110/in.2025.25.e9","url":null,"abstract":"<p><p>The importance of mitochondrial function in macrophages is well established. Alveolar macrophages (AMs), the tissue-resident macrophages (TRMs) of the lung, are particularly dependent on mitochondria-driven oxidative phosphorylation (OXPHOS) to support their functions and maintain homeostasis. However, the specific genes and pathways that regulate OXPHOS in AMs remain unclear. In this study, we investigated the role of CR6-interacting factor 1 (CRIF1), a mitochondrial regulator, as a key factor that specifically modulates the metabolic fitness and maintenance of AMs. Using single-cell RNA sequencing and transcriptomic analyses, we found CRIF1 to be highly expressed in AMs compared to TRMs from other tissues, correlating with enhanced OXPHOS activity. Genetic ablation of <i>Crif1</i> in macrophages resulted in a marked reduction in AM populations exclusively in the lung, while other TRM populations were unaffected. CRIF1-deficient AMs exhibited an altered metabolic profile, including impaired mitochondrial function, increased glycolysis, and aberrant lipid accumulation. These findings underscore the essential role of CRIF1 in regulating mitochondrial functions and metabolic fitness in AMs, distinguishing it from broader mitochondrial regulators like mitochondrial transcription factor A, which operates across multiple TRM populations. Our study provides critical insights into the tissue-specific regulation of macrophage metabolism and suggests potential therapeutic avenues for lung diseases associated with AM dysfunction.</p>","PeriodicalId":13307,"journal":{"name":"Immune Network","volume":"25 1","pages":"e9"},"PeriodicalIF":4.3,"publicationDate":"2025-02-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11896662/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143614833","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}
Immune NetworkPub Date : 2025-02-14eCollection Date: 2025-02-01DOI: 10.4110/in.2025.25.e10
Hyun-Ki Shin, Ye-Ji Bang
{"title":"Aromatic Amino Acid Metabolites: Molecular Messengers Bridging Immune-Microbiota Communication.","authors":"Hyun-Ki Shin, Ye-Ji Bang","doi":"10.4110/in.2025.25.e10","DOIUrl":"10.4110/in.2025.25.e10","url":null,"abstract":"<p><p>Aromatic amino acid (AAA) metabolites, derived from tryptophan, phenylalanine, and tyrosine through coordinated host and microbial metabolism, have emerged as critical modulators of immune function. We examine the complex journey of AAAs from dietary intake through intestinal absorption and metabolic transformation, highlighting the crucial role of host-microbe metabolic networks in generating diverse immunomodulatory compounds. This review provides a unique integrative perspective by mapping the molecular mechanisms through which these metabolites orchestrate immune responses. Through detailed analysis of metabolite-receptor and metabolite-transporter interactions, we reveal how specific molecular recognition drives cell type-specific immune responses. Our comprehensive examination of signaling networks-from membrane receptor engagement to nuclear receptor activation to post-translational modifications- demonstrates how the same metabolite can elicit distinct functional outcomes in different immune cell populations. The context-dependent nature of these molecular interactions presents both challenges and opportunities for therapeutic development, particularly in inflammatory conditions where metabolite signaling pathways are dysregulated. Understanding the complexity of these regulatory networks and remaining knowledge gaps is fundamental for advancing metabolite-based therapeutic strategies in immune-mediated disorders.</p>","PeriodicalId":13307,"journal":{"name":"Immune Network","volume":"25 1","pages":"e10"},"PeriodicalIF":4.3,"publicationDate":"2025-02-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11896664/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143614801","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}
Immune NetworkPub Date : 2025-02-12eCollection Date: 2025-02-01DOI: 10.4110/in.2025.25.e8
Tzu-Hsuan Chang, Ping-Chih Ho
{"title":"Interferon-driven Metabolic Reprogramming and Tumor Microenvironment Remodeling.","authors":"Tzu-Hsuan Chang, Ping-Chih Ho","doi":"10.4110/in.2025.25.e8","DOIUrl":"10.4110/in.2025.25.e8","url":null,"abstract":"<p><p>IFNs play a critical role in cancer biology, including impacting tumor cell behavior and instructing the tumor microenvironment (TME). IFNs recently have been shown to reprogram tumor metabolism through distinct mechanisms. Furthermore, IFNs shape the TME by modulating immune cell infiltration and function, contributing to the intricate interaction between the tumor and stromal cells. This review summarizes the effects of IFNs on metabolic reprogramming and their impacts on the function of immune cells within the TME, with a particular focus on the dual roles of IFNs in mediating both anti-tumor and pro-tumor immune responses. Understanding the significance of IFNs-mediated processes aids to advise future therapeutic strategies in cancer treatment.</p>","PeriodicalId":13307,"journal":{"name":"Immune Network","volume":"25 1","pages":"e8"},"PeriodicalIF":4.3,"publicationDate":"2025-02-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11896656/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143614829","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}
Immune NetworkPub Date : 2025-02-11eCollection Date: 2025-02-01DOI: 10.4110/in.2025.25.e6
Naeyoon Jang, Il-Kyu Kim, Dawoon Jung, Yeonseok Chung, Yun Pyo Kang
{"title":"Regulation of Ferroptosis in Cancer and Immune Cells.","authors":"Naeyoon Jang, Il-Kyu Kim, Dawoon Jung, Yeonseok Chung, Yun Pyo Kang","doi":"10.4110/in.2025.25.e6","DOIUrl":"10.4110/in.2025.25.e6","url":null,"abstract":"<p><p>Ferroptosis, an iron-dependent form of regulated cell death, is driven by lipid peroxidation and shaped by metabolic and antioxidant pathways. In immune cells, ferroptosis susceptibility varies by cell types, lipid composition, and metabolic demands, influencing immune responses in cancer, infections, and autoimmune diseases. Therapeutically, targeting ferroptosis holds promise in cancer immunotherapy by enhancing antitumor immunity or inhibiting immunosuppressive cells. This review highlights the metabolic pathways underlying ferroptosis, its regulation in immune cells, its dual role in tumor progression and antitumor immunity, and its context-dependent therapeutic implications for optimizing cancer treatment.</p>","PeriodicalId":13307,"journal":{"name":"Immune Network","volume":"25 1","pages":"e6"},"PeriodicalIF":4.3,"publicationDate":"2025-02-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11896659/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143614838","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}
Immune NetworkPub Date : 2025-02-07eCollection Date: 2025-02-01DOI: 10.4110/in.2025.25.e3
Jongho Ham, Wooseok Yang, Hye Young Kim
{"title":"Tissue-Specific Metabolic Reprogramming in Innate Lymphoid Cells and Its Impact on Disease.","authors":"Jongho Ham, Wooseok Yang, Hye Young Kim","doi":"10.4110/in.2025.25.e3","DOIUrl":"10.4110/in.2025.25.e3","url":null,"abstract":"<p><p>Recent advances have highlighted the crucial role of metabolic reprogramming in shaping the functions of innate lymphoid cells (ILCs), which are vital for tissue immunity and homeostasis. As tissue-resident cells, ILCs dynamically respond to local environmental cues, with tissue-derived metabolites such as short-chain fatty acids and amino acids directly modulating their effector functions. The metabolic states of ILC subsets-ILC1, ILC2, and ILC3-are closely linked to their ability to produce cytokines, sustain survival, and drive proliferation. This review provides a comprehensive analysis of how key metabolic pathways, including glycolysis, oxidative phosphorylation, and fatty acid oxidation, influence ILC activation and function. Furthermore, we explore the complex interactions between these metabolic pathways and tissue-specific metabolites, which can shape ILC-mediated immune responses in health and disease. Understanding these interactions reveals new insights into the pathogenesis of conditions such as asthma, inflammatory bowel disease, and cancer. A deeper understanding of these mechanisms may not only advance our knowledge of disease pathogenesis but also lead to the development of novel therapeutic strategies targeting metabolic pathways in ILCs to treat tissue-specific immune disorders.</p>","PeriodicalId":13307,"journal":{"name":"Immune Network","volume":"25 1","pages":"e3"},"PeriodicalIF":4.3,"publicationDate":"2025-02-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11896661/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143614805","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}