Immunology letters最新文献

{"title":"A shared monocyte cytokine signature induced by serum from patients with systemic lupus erythematosus and anti-MDA5 antibody-positive dermatomyositis through the type I interferon pathway.","authors":"Shohei Nakamura, Yuko Okamoto, Hideto Takada, Yasuhiro Katsumata, Masayoshi Harigai","doi":"10.1016/j.imlet.2025.107066","DOIUrl":"10.1016/j.imlet.2025.107066","url":null,"abstract":"<p><strong>Objectives: </strong>To investigate the cytokine induction profile across multiple myeloid lineages by sera from patients with systemic lupus erythematosus (SLE) or polymyositis/dermatomyositis (PM/DM) using ex vivo whole blood stimulation assay and identify the signaling pathway relevant to monocyte cytokine signature.</p><p><strong>Methods: </strong>Serum samples were obtained from adult patients with SLE, anti-melanoma differentiation-associated gene 5 (MDA5)-positive DM, anti-aminoacyl tRNA synthetase (ARS)-positive PM/DM, and healthy controls. Heparinized whole blood from healthy donors was incubated with serum, IFN-α, and IFN-β, followed by flow cytometric analysis. The expression of 9 cytokines was analyzed in CD14⁺ monocytes. The effect of upadacitinib preincubation on cytokine induction was evaluated. CD14⁺ monocytes isolated from healthy donors were incubated with serum or IFN-β, followed by bulk RNA sequencing.</p><p><strong>Results: </strong>Active SLE and MDA5 sera induced a shared monocyte cytokine signature with upregulation of monocyte chemoattractant protein-1 (MCP1) and interleukin-1 receptor antagonist (IL-1RA) in CD14⁺ monocytes, whereas ARS and control sera did not. This monocyte cytokine signature closely resembled that induced by IFN-α and IFN-β. RNA-seq revealed 383 upregulated genes common to SLE serum, MDA5 serum, and IFN-β. Pathway analysis revealed that genes upregulated by exposure to SLE serum and MDA5 serum were predominantly involved in IFN-αβ signaling pathway. Upadacitinib abrogated the monocyte cytokine signature induced by SLE or MDA5 serum.</p><p><strong>Conclusions: </strong>Serum from patients with active SLE and anti-MDA5+ DM can induce a shared monocyte cytokine signature, primarily through the IFN-αβ signaling pathway. CD14⁺ monocytes \"primed\" by serum may contribute to the pathogenesis of these diseases.</p>","PeriodicalId":13413,"journal":{"name":"Immunology letters","volume":" ","pages":"107066"},"PeriodicalIF":2.8,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144804007","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The cancer-immunity cycle in motion: The effects of exercise on antitumor immunity.","authors":"Katharina Leuchte, Maike Trommer, Gitte Holmen Olofsson, Per Thor Straten","doi":"10.1016/j.imlet.2025.107101","DOIUrl":"https://doi.org/10.1016/j.imlet.2025.107101","url":null,"abstract":"<p><p>Physical activity has recently emerged as a promising modulator of antitumor immunity, but the underlying mechanisms are incompletely understood. Here, we review human studies assessing the effects of exercise on the single steps of the cancer-immunity cycle. Interventions were mostly based on acute or continuous high- and moderate-intensity endurance exercise, followed by analyses of immune cell function and serum markers. There is evidence that exercise enhances tumor cell susceptibility to apoptosis and promotes dendritic cell maturation via damage-associated molecular patterns. Catecholamine-mediated NK and CD8⁺ T cell mobilization facilitates trafficking to tumors, further supported by vascular and metabolic changes to the tumor microenvironment. Overall, there is evidence from human studies that exercise improves immune cell effector function at different steps of the cancer-immunity cycle, thereby potentiating antitumor responses. These findings support the integration of structured exercise therapy into cancer care, possibly in combination with immunotherapeutic strategies. Further mechanistic and clinical research is warranted to optimize exercise-based interventions.</p>","PeriodicalId":13413,"journal":{"name":"Immunology letters","volume":" ","pages":"107101"},"PeriodicalIF":2.8,"publicationDate":"2025-10-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145250915","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Profiling of circulating T follicular helper and T peripheral helper cell subsets in patients with primary biliary cholangitis.","authors":"Haixia Ma, Ying Liu, Yuehong Zhu, Guoxin Xu, Xiaoli Xiang, Senlin Xue, Zhicheng Zhang, Cuie Cheng, Fenying Lu, Bin Wang, Yanyun Zhang, Tingwang Jiang","doi":"10.1016/j.imlet.2025.107100","DOIUrl":"10.1016/j.imlet.2025.107100","url":null,"abstract":"<p><p>Primary biliary cholangitis (PBC) is a common chronic cholestatic autoimmune liver disease that may progress to liver fibrosis or cirrhosis if not accurately diagnosed and promptly treated. T follicular helper (Tfh) cells and T peripheral helper (Tph) cells, as subsets of T cells that assist B cells in producing antibodies, are closely related to the pathogenesis of autoimmune diseases. This research aims to explore the potential of Tfh and Tph cells as biomarkers for PBC disease progression. We recruited 30 PBC patients, 25 post-hepatitis B cirrhosis (PHBC) patients, and 30 healthy subjects. Both Tfh and Tph cells were significantly enriched in the peripheral blood of PBC patients, and their frequencies were correlated with autoantibody production. Area under the ROC curve (AUC) analysis demonstrated that Tfh and Tph cell frequencies exhibited convergent diagnostic performance with anti-mitochondrial antibody (AMA) in discriminating PBC patients from healthy controls. Furthermore, the frequencies of these cells were positively correlated with liver enzyme levels (ALT, AST, and GGT), suggesting that they may indicate liver and bile duct damage in PBC patients. The frequency of Tfh cells was negatively correlated with total protein (TP) and albumin (ALB) levels, indicating that the increase of Tfh cells was related to the impairment of hepatocyte function. Additionally, the frequencies of Tfh and Tph cells were positively correlated with IgM levels, showing that these cells seem to be involved in the production of immunoglobulins. Together, Tfh and Tph cells can serve as biomarkers for both diagnosing PBC and correlating with disease severity.</p>","PeriodicalId":13413,"journal":{"name":"Immunology letters","volume":" ","pages":"107100"},"PeriodicalIF":2.8,"publicationDate":"2025-10-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145232481","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Immunological features driving distinct repigmentation patterns in patients with stable vitiligo submitted to the autologous keratinocyte/melanocyte transplantation.","authors":"Bruna Estefânia Diniz Frias, Roberta Oliveira Prado, Mariana Gontijo Ramos, Nathália Werneck Cézar de Oliveira, Fernanda Fortes de Araújo, Liliane Martins Dos Santos, Camila Gontijo Ramos, Camila Bechara Kallás, Maria Sílvia Laborne Alves de Sousa, Ismael Artur Costa-Rocha, Joaquim Pedro Brito-de-Sousa, Rachel Basques Caligiorne, Marcelo Antônio Pascoal-Xavier, Vanessa Peruhype-Magalhães, Daniel Gontijo Ramos, Andréa Teixeira-Carvalho, Olindo Assis Martins-Filho","doi":"10.1016/j.imlet.2025.107098","DOIUrl":"https://doi.org/10.1016/j.imlet.2025.107098","url":null,"abstract":"<p><p>This study aimed to characterize biomarkers of therapeutic response in patients with stable vitiligo undergoing the autologous non-cultured keratinocyte/melanocyte transplantation. The approaches performed were systemic analysis evaluated during pre-transplantation/(D0), seven/(D7), and 28/(D28-45) days after the procedure and compartmentalized analysis in epidermal cell suspension (explant). Increased number of pro-inflammatory monocytes and NK-cells was found during the transplantation follow-up in vitiligo patients compared to the control. There were higher numbers of CD8+ T-cells and CD4+HLA-DR+ T-cells circulating at D28-45 compared to D0, and increased number of CD8+HLA-DR+ T-cells at D28-45 compared to D7. Decreased levels of the most pro-inflammatory chemokines/cytokines during post-transplantation kinetics timeline were observed. Integrative analysis demonstrated that patients with unsatisfactory repigmentation presented higher numbers of connections between the blood/skin components at D0. The data suggest differentiated profiles in the dynamics of the hematological/immunological biomarkers, according to the kinetics timeline and the clinical outcome of repigmentation in vitiligo patients.</p>","PeriodicalId":13413,"journal":{"name":"Immunology letters","volume":" ","pages":"107098"},"PeriodicalIF":2.8,"publicationDate":"2025-10-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145228437","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"CD4 and CD8 T-cell Lymphocytes from Penile Squamous Cell Carcinoma Tumors are more Differentiated with higher PD-1 Expression compared to Lymphocytes in Peripheral Circulation.","authors":"Chibamba Mumba, Nicholas K Mwale, Victor Mapulanga, Owen Ngalamika","doi":"10.1016/j.imlet.2025.107099","DOIUrl":"https://doi.org/10.1016/j.imlet.2025.107099","url":null,"abstract":"<p><strong>Background: </strong>Penile squamous cell carcinoma (PSCC) is the commonest malignancy of the penis, with a higher incidence and poor treatment outcomes in developing countries. T-cell phenotypes have been shown to identify patients who may respond favorably to immune therapy, and also associate with treatment outcomes. This study aimed to determine and compare the tumor and peripheral blood T-cell phenotypes of individuals with PSCC, and whether factors such as smoking and presence of HPV associate with these T-cell phenotypes.</p><p><strong>Methods: </strong>We conducted a prospective cross-sectional study at the University Teaching Hospital, Lusaka, Zambia. Participants with a histologically-confirmed PSCC were recruited into the study. Socio-demographic information was obtained, and whole blood was collected and subjected to peripheral blood mononuclear cells (PBMCs) isolation. Fresh penile tumors were mechanically and enzymatically digested. CD4 and CD8 cells were sorted from PBMCs and tumor, stained using antibodies against CD3, CD45RO, CCR7, PD-1, CD103 and CD69, and subjected to flow cytometry. Parts of the tumor were subjected to HPV detection, and histological grading and staging.</p><p><strong>Results: </strong>Twenty-four participants were recruited into the study. The median age was 55.5 years, 45.8% were smokers, 87.5% were HIV positive, 62.5% had high-risk HPV detected in the tumors, and 25% had advanced-stage disease. There was a significantly higher proportion of naïve cells among CD4 T-cells from PBMCs than tumor (40.2% vs 3.8%; p=0.01). CD4 T cells from the tumor demonstrated a significantly higher proportion of cells expressing CD69 (3.2% vs 95.9%; p=0.0001), CD103 (0.7% vs 7.3%; p=0.0001), and PD-1 (35.5% vs 92%; p=0.0001) than the ones from PBMCs. Tumoral CD8 T-cells had a significantly lower proportion of terminally-differentiated effector cells but higher proportion of central memory cells compared to PBMCs, (7.9% vs 15.1%, p=0.04) and (55% vs 14.4%; p=0.01) respectively. Tumoral CD8 T-cells also had a significantly higher proportion of cells expressing CD69 (96.7% vs 8.5%; p=0.0001), CD103 (22.2% vs 1.2%; p=0.0001), and PD-1 (79.3% vs 18.8%; p=0.0001) when compared to the PBMCs. Early-stage disease was associated with a significantly higher proportion of central memory CD4 T-cells among the PBMCs when compared with advanced stage disease (46.7% vs 30%; p=0.01), while smoking was associated with a significantly higher proportion of tumoral CD8 T-cells expressing the homing marker CD103 (28.2% vs 17.8%; p=0.01).</p><p><strong>Conclusion: </strong>PSCC tumors demonstrate a higher proportion of primed T-cells with a memory phenotype compared to T-cells in the circulation. T-cells from PSCC tumors also have a higher proportion of cells expressing the immune checkpoint PD-1 and homing markers than those from the circulation.</p>","PeriodicalId":13413,"journal":{"name":"Immunology letters","volume":" ","pages":"107099"},"PeriodicalIF":2.8,"publicationDate":"2025-10-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145228256","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Taurohyodeoxycholic acid ameliorates inflammatory response in a murine model of ovalbumin (OVA)-induced allergic asthma","authors":"Ye You ,&nbsp;Jing Li ,&nbsp;Jiayi Wang ,&nbsp;Xianglan Luo ,&nbsp;Jingyuan Liu ,&nbsp;Xinmiao Wang ,&nbsp;Shichen Yi ,&nbsp;Ruizhi He ,&nbsp;Yating Shi ,&nbsp;Jie Xu ,&nbsp;Mengqing Hou ,&nbsp;Yanjun Cao ,&nbsp;Yang Li ,&nbsp;Jing Dong ,&nbsp;Jiao He","doi":"10.1016/j.imlet.2025.107096","DOIUrl":"10.1016/j.imlet.2025.107096","url":null,"abstract":"<div><div>Taurohyodeoxycholic acid (THDCA), a naturally occurring conjugated bile acid compound formed by the condensation of taurine and deoxycholic acid, possesses various biological activities. Present study attempted to assess whether THDCA can alleviate airway inflammation in allergic asthma through regulating the immune balance among CD4⁺ <em>T</em> cell subgroups. Mice were exposed with ovalbumin (OVA) to build allergic asthma model and THDCA was administrated orally. Pulmonary histopathology analysis was evaluated by H&amp;E and PAS staining. The typical cytokines and transcription factors of CD4⁺ <em>T</em> cell subgroups were determined, and the proportion of CD4⁺ <em>T</em> cell subgroups were analyzed. The oral administration of THDCA attenuated OVA-induced asthma by decreasing inflammatory cell counts in the bronchoalveolar lavage fluid (BALF), reducing tIgE and OVA-sIgE concentration in the serum, and improving histopathological changes in the lung tissue. In addition, THDCA reduced the secretion of IL-4, IL-5, IL-13, IL-6, TNF-α, IL-17A, and TGF-β1, but increased the production of IFN-γ, IL-10, and IL-35 in the BALF and lung tissue. Meanwhile, THDCA inhibited GATA3 and RORγt expression, and STAT3 phosphorylation, but improved T-bet and Foxp3 expression in the lung tissue. Besides, THDCA restored the proportion of CD4⁺ <em>T</em> cell subgroups in the spleen and peripheral blood. These findings indicated that THDCA may have therapeutic potential for treating allergic asthma by regulating the immune balance of CD4⁺ <em>T</em> cell subgroups.</div></div>","PeriodicalId":13413,"journal":{"name":"Immunology letters","volume":"277 ","pages":"Article 107096"},"PeriodicalIF":2.8,"publicationDate":"2025-09-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145185759","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Restoration of Fli1 expression as a potential therapeutic approach in Systemic Sclerosis: Effects on age-associated B cells","authors":"Athanasios Sachinidis ,&nbsp;Malamatenia Lamprinou ,&nbsp;Theodoros Dimitroulas","doi":"10.1016/j.imlet.2025.107094","DOIUrl":"10.1016/j.imlet.2025.107094","url":null,"abstract":"<div><div>Fli1 is a transcription factor playing a major role in the regulation of normal hematopoiesis and vasculogenesis. Its deficiency has been associated with the development of fibrosis in various diseases, including systemic sclerosis/scleroderma (SSc), a rare autoimmune rheumatic disease. In addition, in <em>Fli1</em> B cell conditional knockout mice, a striking increase of age-associated B cells (ABCs) has been observed. These cells constitute a CD11c⁺CD21^low/- B cell population that displays an expansion in autoimmunity and drives disease pathogenesis. The exact role and functions of ABCs, though, are not yet fully understood. Taking into consideration all the above, regarding Fli1 deficiency in SSc pathogenesis and ABC expansion, we propose restoration of this specific transcription factor’s expression as a potential therapeutic approach for the aforementioned rheumatic disease. Moreover, we provide some interventions that aim to restore Fli1 expression via modulating the signals of TGF-β pathway, whose activation is considered as crucial for fibrosis development in SSc.</div></div>","PeriodicalId":13413,"journal":{"name":"Immunology letters","volume":"277 ","pages":"Article 107094"},"PeriodicalIF":2.8,"publicationDate":"2025-09-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145185729","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Tryptophan metabolism in health and disease- implications for non-communicable diseases","authors":"Andiswa Msizi Gabela,&nbsp;Nontobeko Mthembu,&nbsp;Sabelo Hadebe","doi":"10.1016/j.imlet.2025.107093","DOIUrl":"10.1016/j.imlet.2025.107093","url":null,"abstract":"<div><div>Tryptophan, an essential amino acid, is primarily metabolized through four key pathways: the kynurenine pathway, serotonin pathways, indole pathways and interleukin 4-induced gene 1 (IL-4I1) pathways. Dysregulation of tryptophan metabolism is implicated in various non-communicable diseases including psychiatric disorders, inflammatory and autoimmune diseases, as well as metabolic diseases. The dogma in the field is that tryptophan is metabolized via the kynurenine pathway in the liver mainly by indoleamine 2,3-dioxygenase 1/2 (IDO 1/2) and Tryptophan dioxygenase 2 (TDO2) enzymes. However, there is growing evidence demonstrating that IL-4I1 and tryptophanase are also crucial tryptophan catabolizing enzymes resulting in metabolites that activate aryl hydrocarbon receptor (AhR) and modulate immune responses. Tryptophan metabolism is crucial in cellular, tissue and organismal function and its disruption is linked to conditions such as inflammatory bowel disease (IBD), multiple sclerosis (MS), and psychiatric disorders like depression, anxiety and metabolic diseases such as obesity and Type 2 diabetes. It is unclear though whether only specific tryptophan pathways are associated with disease or there is a level of redundancy. Some key metabolites from tryptophan catabolism can come from multiple pathways, with opposing or converging effects on cellular functions. This review will explore the critical role of tryptophan metabolism in health and diseases, focusing on its implications in non-communicable diseases. Importantly, this review will focus on recent developments in tryptophan metabolism and strengthen the argument for a revised schematic tryptophan catabolic pathway.</div></div>","PeriodicalId":13413,"journal":{"name":"Immunology letters","volume":"277 ","pages":"Article 107093"},"PeriodicalIF":2.8,"publicationDate":"2025-09-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145182024","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Beyond HNA-1: The Anti-HNA-3 Autoantibody as a Protagonist in Autoimmune Neutropenia.","authors":"Renato Cerqueira, Elyse Moritz, Josefina A P Braga, Akemi K Chiba, João B Pesquero, José O Bordin","doi":"10.1016/j.imlet.2025.107095","DOIUrl":"https://doi.org/10.1016/j.imlet.2025.107095","url":null,"abstract":"<p><strong>Introduction: </strong>Autoimmune neutropenia (AIN), a common cause of chronic neutropenia, has been categorized as primary (pAIN) and secondary (sAIN). This study investigates the specificity of anti-HNA autoantibodies in both types.</p><p><strong>Materials and methods: </strong>A prospective cohort study of 85 chronic neutropenia patients included those with detectable anti-HNA autoantibodies. Anti-HNA was assessed using granulocyte agglutination (GAT), granulocyte immunofluorescence (GIFT), and LABScreen Multi Kit (LSM). Molecular analysis was performed to assess HNA expression.</p><p><strong>Results: </strong>Of 85 patients, 7 had pAIN and 8 had sAIN. All pAIN patients exhibited only anti-HNA-1, while anti-HNA-3 was found in 3/8 sAIN patients. All patients with anti-HNA-3 tested positive in LSM; one was positive in both GAT and GIFT.</p><p><strong>Discussion: </strong>While anti-HNA-3 has been described exclusively as an alloantibody, this is the first report of anti-HNA-3 as an autoantibody in AIN.</p><p><strong>Conclusion: </strong>Anti-HNA-3 autoantibody is associated only with sAIN, suggesting distinct mechanisms in pAIN and sAIN.</p>","PeriodicalId":13413,"journal":{"name":"Immunology letters","volume":" ","pages":"107095"},"PeriodicalIF":2.8,"publicationDate":"2025-09-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145182017","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Fatty acid binding protein 2 (FATP2/SLC27A2) blockade with Lipofermata elicits dual effects on inflammatory responses in human monocytes and macrophages","authors":"Nico Hahn ,&nbsp;Serhii Chornyi ,&nbsp;Daan Heister ,&nbsp;Helga E. de Vries ,&nbsp;Martin Giera ,&nbsp;Mariëtte R. Boon ,&nbsp;Gijs Kooij ,&nbsp;Jan Van den Bossche","doi":"10.1016/j.imlet.2025.107092","DOIUrl":"10.1016/j.imlet.2025.107092","url":null,"abstract":"<div><div>Inflammatory responses often involve metabolic rewiring within immune cells to support effector functions. Targeting metabolic pathways in immune cells therefore represents a promising strategy to modulate inflammatory diseases and improve therapeutic outcomes. Acyl-CoA synthesis by fatty acid transporter 2 (FATP2/SLC27A2) facilitates the transport of long-chain fatty acids into the cell. It represents a key step in fatty acid metabolism and the subsequent production of bioactive lipid mediators (LMs) with immunoregulatory functions. While the FATP2 inhibitor Lipofermata is currently evaluated for lipid-lowering therapies in metabolic diseases, and to revert the suppressive nature of myeloid cells in cancer, its effect on inflammatory responses in human macrophages remains elusive.</div><div>Here, we show that Lipofermata reduced LPS-induced inflammatory responses in whole blood and human monocytes. This anti-inflammatory effect was paralleled by a decreased biosynthesis of arachidonic acid-derived inflammatory LMs, including prostaglandin E2 (PGE2) and thromboxane 2 (TxB2). These findings suggest an anti-inflammatory effect mediated by Lipofermata-mediated redirection of lipid metabolism in monocytes.</div><div>Conversely, in mature human monocyte-derived macrophages, Lipofermata treatment enhanced LPS-induced cytokine production and induced cell death, likely through inflammasome activation. Together, these results underscore the cell type-specific effects of FATP2 inhibition and highlight the dual role of Lipofermata in modulating inflammatory immune responses. As such, targeting lipid metabolism with Lipofermata could have therapeutic potential with both anti- and pro-inflammatory applications, depending on the target cell type and context.</div></div>","PeriodicalId":13413,"journal":{"name":"Immunology letters","volume":"277 ","pages":"Article 107092"},"PeriodicalIF":2.8,"publicationDate":"2025-09-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145182068","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}