Cellular immunology最新文献

{"title":"Characterization of lysate from NK-92 cells and its potential use as an immunotherapeutic modality","authors":"Himani Chinnapen ,&nbsp;Laurent Boissel ,&nbsp;Courtney Fleenor ,&nbsp;Thomas Bickett ,&nbsp;Zhimin Guo ,&nbsp;Vidya Godbole ,&nbsp;Manju Saxena ,&nbsp;Patrick Soon-Shiong ,&nbsp;Hans Klingemann","doi":"10.1016/j.cellimm.2025.104951","DOIUrl":"10.1016/j.cellimm.2025.104951","url":null,"abstract":"<div><div>Lysates from human cells represent biofluids that are used in the biotechnology field for a number of reasons such as biomarker identification and antibody detection. Lysate from human blood platelets is widely used in the clinical setting to control bleeding. We hypothesized that the lysate from the cytotoxic natural killer cell line NK-92® should contain perforin and proteolytic enzymes in addition to immunomodulatory cytokines, all of which have biological relevance and could be used for local treatment of cancer lesions. Here lysate from <em>NK-92 (aNK™)</em> cells, and its erIL-2 engineered variant <em>haNK™</em> was obtained by repeat freeze/thawing. Immunoblot, ELISA and cytokine immunoassay analysis confirmed the presence of perforin and the full spectrum of granzymes, as well as of various chemokines and cytokines known to be expressed in NK-92 cells. Lysate from haNK cells displayed cytotoxic and anti-proliferative activity against human and canine cancer cell lines after only a 15-min exposure in vitro. Importantly, under the same conditions the lysate did not affect primary cells. Intra-tumor injection of haNK lysate into intradermal tumors of immunocompetent C57BL/6 mice provided tumor control in 40 % of treated animals. When re-challenged with the same tumor line several weeks after primary tumor clearance, no growth occurred indicating that intra-tumor administration of haNK lysate can generate a vaccine-like effect.</div></div>","PeriodicalId":9795,"journal":{"name":"Cellular immunology","volume":"413 ","pages":"Article 104951"},"PeriodicalIF":3.7,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143928531","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":"Integrated proteomics and phosphoproteomics profiling dynamic signaling networks underlying two distinct types of macrophage activation","authors":"Lihong Wu ,&nbsp;Hang Xu ,&nbsp;Xiaonan Zhang ,&nbsp;Minghui Zhang ,&nbsp;Yuting Xu ,&nbsp;Qianyue Zhang ,&nbsp;Huiying Tao ,&nbsp;Changming Dong ,&nbsp;Xinxin Zhang ,&nbsp;Mingming Zhou ,&nbsp;Jinbo Yang ,&nbsp;Chunhua Lin ,&nbsp;Qiaoling Song","doi":"10.1016/j.cellimm.2025.104972","DOIUrl":"10.1016/j.cellimm.2025.104972","url":null,"abstract":"<div><div>Macrophages play a crucial role in antimicrobial host defense and those with differential maturation/differentiation status differ in inflammatory responses. Herein, GM-CSF and M-CSF primed mouse bone marrow derived macrophages (GM-BMDMs, GM and M-BMDMs, M), the well-established macrophage models in vitro, were utilized and their dynamic signaling changes in response to gram-negative bacteria component LPS treatment were analyzed using both 4D label-free proteomics and phosphoproteomics. Protein changes maintained relatively constant within or across GM and M macrophages post LPS challenge while phospho-protein exhibited more diverse and transient changes. Early induction of phospho-mediated GTPase activities, mRNA processing, and protein-mediated metabolic changes like oxidative phosphorylation (OXPHOS)/mitochondria function was identified at 1 h and maintained until 6 h post LPS treatment in GM and M while canonical TLR mediated MyD88-dependent and -independent pathways were activated at 3 and 6 h, individually at protein levels. Classical and novel phospho-sites for MyD88 and TRIF signaling pathways were also detected by phosphoproteomics. Comprehensively, the integrated protein and phospho-protein trend analysis was conducted and the core protein-phospho-protein network for the early phase actin reorganization, phagocytosis, and TLR signaling in both GM and M were presented. Taken together, these data described differences and similarities between these two types of macrophages in terms of their inflammatory responses to LPS.</div></div>","PeriodicalId":9795,"journal":{"name":"Cellular immunology","volume":"413 ","pages":"Article 104972"},"PeriodicalIF":3.7,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144088678","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":"Divergent impact of endotoxin priming and endotoxin tolerance on macrophage responses to cancer cells","authors":"Konkonika Roy ,&nbsp;Tomasz Jędrzejewski ,&nbsp;Justyna Sobocińska ,&nbsp;Paulina Spisz ,&nbsp;Bartosz Maciejewski ,&nbsp;Nadine Hövelmeyer ,&nbsp;Benedetta Passeri ,&nbsp;Sylwia Wrotek","doi":"10.1016/j.cellimm.2025.104934","DOIUrl":"10.1016/j.cellimm.2025.104934","url":null,"abstract":"<div><div>Endotoxin tolerance (ET) is an adaptive phenomenon that arises from the repeated exposure of immune cells, such as macrophages, to endotoxins like lipopolysaccharide (LPS). Initially, when macrophages are activated by LPS, they produce inflammatory mediators that drive the primary immune response. However, this response is significantly diminished during the establishment of ET, creating an immunosuppressive environment. This environment can facilitate the development and progression of malignant conditions, including cancer.</div><div>Our research focused on the interactions between immune cells and the tumor microenvironment under ET conditions. Through comprehensive <em>in vivo</em> and <em>in vitro</em> studies employing various research techniques, we have demonstrated that interactions between endotoxin-tolerant macrophages (Mo_ET) and cancer cells contribute to a pro-tumorigenic condition. Notably, we observed that Mo_ET adapt a pro-tumorigenic, immunosuppressive M2 phenotype (CD163 expression). These macrophages involves distinct metabolic pathways, not depending solely on glycolysis and oxidative phosphorylation. Furthermore, our <em>in vivo</em> findings revealed macrophage infiltration within tumors under both ET and non-ET conditions, highlighting the suppressed immune landscape in the presence of ET. These findings suggest that ET plays a pivotal role in shaping tumor-associated immune responses and that targeting ET pathways could offer a novel and promising therapeutic approach for cancer treatment.</div></div>","PeriodicalId":9795,"journal":{"name":"Cellular immunology","volume":"411 ","pages":"Article 104934"},"PeriodicalIF":3.7,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143561837","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":"MAPK14 drives Ferroptosis and immune dysfunction in pediatric Sepsis-induced acute lung injury","authors":"Ning Zhang ,&nbsp;Yuanyuan Fan ,&nbsp;Juan Chen ,&nbsp;Juan Gu ,&nbsp;Xiangming Yan","doi":"10.1016/j.cellimm.2025.104948","DOIUrl":"10.1016/j.cellimm.2025.104948","url":null,"abstract":"<div><h3>Objective</h3><div>Sepsis-induced acute lung injury (ALI) is driven by inflammation, oxidative stress, and immune suppression. MAPK14 (p38α) plays a role in ferroptosis and immune regulation, but its specific function in pediatric sepsis remains unclear. Therefore, our study aimed to explore the role and underlying mechanism of MAPK14 in pediatric sepsis.</div></div><div><h3>Methods</h3><div>Bioinformatics analysis of GSE26440 and FerrDb identified ferroptosis-related genes in pediatric sepsis. STRING database was used to predict the proteins associated with MAPK14. MAPK14 expression in whole blood samples, LPS-treated MLE-12 cells, and a CLP mouse model was detected by qRT-PCR and western blot. Ferroptosis was assessed by measuring MDA, GSH, and Fe²⁺ levels, while ROS accumulation was analyzed using DCFH-DA staining and DHE staining. A cycloheximide (CHX) assay was performed to assess TTP53 protein stability. MPO immunohistochemistry and PD-L1 immunofluorescence assessed neutrophil infiltration, and flow cytometry evaluated neutrophil apoptosis.</div></div><div><h3>Results</h3><div>Bioinformatics analysis of GSE26440 and FerrDb identified MAPK14 as a ferroptosis-related gene in pediatric sepsis. MAPK14 expression was upregulated in sepsis patient samples, LPS-treated MLE-12 cells and CLP mouse lung tissues. Overexpression of MAPK14 led to increased MDA and Fe²⁺ levels, reduced GSH, and elevated ROS fluorescence intensity, confirming its role in promoting ferroptosis. Mechanistically, MAPK14 upregulated TTP53, which in turn suppressed SLC7A11 and GPX4, further driving ferroptosis. MAPK14 overexpression stabilized TTP53 and enhanced its activity. Additionally, MAPK14 enhanced MPO and PD-L1 expression to promote neutrophil infiltration and immune suppression. Additionally, MAPK14 overexpression inhibited neutrophil apoptosis, promoted neutrophil infiltration and enhanced immune suppression.</div></div><div><h3>Conclusion</h3><div>MAPK14 drives ferroptosis via the TTP53/SLC7A11/GPX4 pathway and exacerbates immune suppression by promoting neutrophil infiltration.</div></div>","PeriodicalId":9795,"journal":{"name":"Cellular immunology","volume":"411 ","pages":"Article 104948"},"PeriodicalIF":3.7,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143807608","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":"A new chimeric protein composed by T-cell epitopes from peroxidoxin and pyridoxal kinase proteins is protective against visceral leishmaniasis","authors":"Daniela P. Lage ,&nbsp;Danniele L. Vale ,&nbsp;Marcela G.P. Silva ,&nbsp;Vívian T. Martins ,&nbsp;Ana A.M. Gonçalves ,&nbsp;Kamila A. Silva ,&nbsp;Gabriel J.L. Moreira ,&nbsp;Rafaela D. Olegário ,&nbsp;Flávia C. Rizzatti ,&nbsp;Camila S. Freitas ,&nbsp;Breno L. Pimenta ,&nbsp;Karolina O.M. Falcão ,&nbsp;Saulo S.G. Dias ,&nbsp;João A. Oliveira-da-Silva ,&nbsp;Raquel S.B. Câmara ,&nbsp;Isabela A.G. Pereira ,&nbsp;Miguel A. Chávez-Fumagalli ,&nbsp;Bruno M. Roatt ,&nbsp;Ricardo A. Machado-de-Ávila ,&nbsp;Alexsandro S. Galdino ,&nbsp;Eduardo A.F. Coelho","doi":"10.1016/j.cellimm.2025.104949","DOIUrl":"10.1016/j.cellimm.2025.104949","url":null,"abstract":"<div><div>Visceral leishmaniasis (VL) is a neglected tropical disease caused by intracellular protozoan parasites, and which present high incidence in populations in the world. The diagnosis is difficult to be performed, and treatment is toxic and/or presents high cost. In this context, prophylactic vaccination could help as an effective control measure against the disease. In this study, a new chimeric protein (LAV) was constructed with immunogenic T-cell epitopes from two immunogenic <em>Leishmania</em> proteins, and it was evaluated to protects BALB/c mice against <em>Leishmania infantum</em> infection. For this, animals were vaccinated with rLAV associated with micelles (Mic) or monophosphoryl lipid A (MPLA) as adjuvants; while the others received saline, rLAV, Mic or MPLA as controls. Results showed that the rLAV/Mic and rLAV/MPLA combinations induced higher cell proliferation indexes in stimulated cell cultures after infection, as well as the development of a polarized Th1-type cellular and humoral response before and after infection, which was based on the production of IFN-γ, IL-12, TNF-α, nitrite, and IgG2a isotype antibodies. In addition, both CD4⁺ and CD8⁺ T-cell subtypes were important for the IFN- secretion in both groups, as compared to the others. Control groups mice produced significantly higher levels of IL-4, IL-10 and anti-parasite IgG1 antibodies, suggesting the occurrence of a Th2-type immune profile in these unprotected animals. The parasite load was found to be significantly lower in mice vaccinated with rLAV/MPLA or rLAV/Mic, as compared to the others, by using a limiting dilution assay and qPCR. In conclusion, data suggest that rLAV plus adjuvant could be considered as a vaccine candidate in future studies to protect against VL.</div></div>","PeriodicalId":9795,"journal":{"name":"Cellular immunology","volume":"411 ","pages":"Article 104949"},"PeriodicalIF":3.7,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143791384","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":"miRNA-186-5p modulates placental inflammation via Inflammasome activation in gestational diabetes mellitus","authors":"Bhatnagar Megha ,&nbsp;K.L. Milan ,&nbsp;M. Anuradha ,&nbsp;Kunka Mohanram Ramkumar","doi":"10.1016/j.cellimm.2025.104959","DOIUrl":"10.1016/j.cellimm.2025.104959","url":null,"abstract":"<div><div>Inflammasomes are multiprotein complexes that initiate inflammatory responses by activating pro-inflammatory cytokines, playing a crucial role in innate immunity. However, their dysregulation can lead to excessive inflammation, particularly in conditions like gestational diabetes mellitus (GDM), where placental inflammation may adversely affect fetal development and increase the risk of complications. NEK7 (NIMA-related kinase 7) has been identified as a key mediator in inflammasome activation, facilitating the complex assembly and amplifying inflammatory responses. This study aims to investigate the regulatory role of miRNA in inflammasome-mediated placental inflammation through its interaction with <em>NEK7</em> in the pathophysiology of GDM. <em>In-silico</em> analysis identified that <em>NEK7</em> is a direct target of miR-186-5p, while PCR analysis demonstrated a significant loss of miR-186-5p expression in GDM placental tissues. Further, the expressions of <em>NEK7, NLRP1, NLRP3</em>, Caspase 1 along with the inflammatory cytokines were significantly elevated in GDM placenta. Furthermore, the correlation analysis demonstrated a significant negative correlation between miR-186-5p and NEK7 expression levels, suggesting that the loss of miR-186-5p may contribute to inflammasome mediated placental inflammation in GDM. Additionally, the overexpression of miR-186-5p decreased the high glucose induced inflammation and the expressions of NEK7, NLRP1 and NLRP3 in BeWo cell line. Therefore, this study concludes that miR-186-5p may attenuate the activation of inflammasome and regulate inflammation via NEK7 in the progression of GDM. Understanding these molecular mechanisms offers valuable insights into potential therapeutic targets aimed at improving pregnancy outcomes in GDM.</div></div>","PeriodicalId":9795,"journal":{"name":"Cellular immunology","volume":"411 ","pages":"Article 104959"},"PeriodicalIF":3.7,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143891535","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":"Transfer of bone marrow niche-residential regulatory T cells ameliorates experimental colitis","authors":"Chen Meng ,&nbsp;Tatsuyuki Sato ,&nbsp;Ryosuke Ueda ,&nbsp;Jiwoo Kim ,&nbsp;Maria Serena Longhi ,&nbsp;Joji Fujisaki","doi":"10.1016/j.cellimm.2025.104952","DOIUrl":"10.1016/j.cellimm.2025.104952","url":null,"abstract":"<div><h3>Background</h3><div>Adoptive transfer of regulatory T cells (Tregs) has been proposed as a next-generation treatment approach for the treatment of various inflammatory or autoimmune disorders(Amini et al., 2022; Bluestone et al., 2023, 2015; Dall'Era et al., 2019; Chandran et al., 2017; Laukova and Glatman Zaretsky, 2023; Voskens et al., 2023; Canavan et al., 2016^1–8), inclusive of inflammatory bowel diseases (IBD). Identification of the appropriate Treg populations as donor sources for effective cell therapy is of great importance. We have recently identified specialized Tregs that localize within the hematopoietic stem cell (HSC) microenvironments(Fujisaki et al., 2011; Hirata et al., 2018, 2019, 2015; Kakiuchi et al., 2021a, 2021b; Furuhashi et al., 2025^9–16) of bone marrow (BM), termed HSC niches. These BM niche Tregs exhibit robust anti-inflammatory and pro-regenerative effects and render HSCs immune privileged. The transfer of BM niche Tregs exhibits high therapeutic effects against BM transplantation and injury(Hirata et al., 2018; Kakiuchi et al., 2021b^{10, 14)}. Yet, the treatment effects of transferred BM niche Tregs in non-BM disease settings remain unknown.</div></div><div><h3>Objectives</h3><div>We investigated the therapeutic effects of transfer of BM niche Tregs for IBD using mouse models of experimental colitis. To identify the key effector molecule of niche Tregs, we further examined the roles of cell-surface ectoenzyme CD39 expressed at high levels by BM niche Tregs.</div></div><div><h3>Study Design</h3><div>Mouse colitis was induced by administering dextran sulfate sodium salt. Subsequently, the mice received intravenous injections of BM niche Tregs, BM non-niche Tregs, lymph node Tregs, or vehicle alone. We compared these treatment effects on clinical scores, histopathological features and profiles of immune cells. We also tested how targeted deletion of CD39 in the adoptively transferred Tregs impacted experimental outcomes.</div></div><div><h3>Results</h3><div>The transfer of as few as 1.5 × 10⁴ BM niche Tregs per mouse ameliorated clinical and histopathological features of the mouse colitis far better than the transfer of other Tregs. The transfer of BM niche Tregs inhibited the generation of Th17 cells and promoted the regeneration and recovery of the colon tissue. Targeted deletion of CD39 in Tregs abrogated therapeutic effects of transferred BM niche Tregs.</div></div><div><h3>Conclusion</h3><div>We show robust therapeutic effects of the transfer of BM niche Tregs in the experimental model of colitis. Donor niche Tregs mediate anti-inflammatory and pro-regenerative effects via Treg CD39. Our work suggests the transfer of BM niche Tregs is a promising approach to treat colitic disorders and boost tissue regeneration.</div></div>","PeriodicalId":9795,"journal":{"name":"Cellular immunology","volume":"411 ","pages":"Article 104952"},"PeriodicalIF":3.7,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143881622","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":"Potential therapeutic strategies targeting efferocytosis for inflammation resolution and tissue repair in inflammatory bowel disease","authors":"Chaoquan Li ,&nbsp;Wanting Liu ,&nbsp;Aoni Fu ,&nbsp;Haotian Yang ,&nbsp;Guanghui Yi","doi":"10.1016/j.cellimm.2025.104957","DOIUrl":"10.1016/j.cellimm.2025.104957","url":null,"abstract":"<div><div>Efferocytosis, the process by which apoptotic cells (ACs) are recognized and cleared by phagocytes, is a critical mechanism in maintaining intestinal immune homeostasis and promoting the resolution of inflammation. Inflammatory bowel disease (IBD), encompassing Crohn's disease (CD) and ulcerative colitis (UC), is characterized by chronic intestinal inflammation, wherein defective efferocytosis contributes to the accumulation of ACs, secondary necrosis, and sustained mucosal damage. This review delineates the molecular mechanisms underlying efferocytosis and systematically examines its functional roles across five key intestinal phagocytic cell types: macrophages, dendritic cells (DCs), neutrophils, intestinal epithelial cells (IECs), and Paneth cells (PCs). Particular emphasis is placed on the dysregulation of efferocytosis capacity in IBD pathogenesis and the consequences of impaired apoptotic cell clearance in both professional and non-professional phagocytes. Furthermore, we evaluate emerging therapeutic strategies designed to restore or enhance efferocytosis, including modulation of macrophage polarization, LC3-associated phagocytosis pathways, nanotechnology-enabled delivery systems, and stem cell-based interventions. A comprehensive understanding of cell-type-specific efferocytosis in the intestinal microenvironment offers promising directions for the development of targeted, inflammation-resolving therapies for IBD.</div></div>","PeriodicalId":9795,"journal":{"name":"Cellular immunology","volume":"411 ","pages":"Article 104957"},"PeriodicalIF":3.7,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143891602","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":"Role of CD44+CCR2+CD64−monocyte-derived macrophage in chronic rhinosinusitis with nasal polyps","authors":"Yuling Zhang ,&nbsp;Mengzhe Yang ,&nbsp;Yan Li ,&nbsp;Zaichuan Wang ,&nbsp;Shujian Zhang ,&nbsp;Limin Zhao ,&nbsp;Yingyue Liu ,&nbsp;Xinyi Li ,&nbsp;Xue Wang ,&nbsp;Feng Lan ,&nbsp;Luo Zhang","doi":"10.1016/j.cellimm.2025.104953","DOIUrl":"10.1016/j.cellimm.2025.104953","url":null,"abstract":"<div><div>Heterogeneity of monocyte-derived macrophages (MDMs) is gradually recognized in polyp tissue of chronic rhinosinusitis with nasal polyps (CRSwNP). However, the contributions of MDM subsets for sustaining inflammation remain unclear. This study therefore aimed to characterize MDM subsets in polyp tissues and estimate their functions. We identified MDM subsets in polyp tissues by flow cytometry, and analyzed the correlation between the expression of these subsets and disease severity. We also explored the similarities and differences between tissue MDMs and classical <em>ex vivo</em> polarized MDMs. By using appropriate substitutes for tissue MDMs, we investigated the function of MDMs. MDM1 (lin⁻CD44⁺CD64⁺) and MDM3 (lin⁻CD44⁺CCR2⁺CD64⁻) were identified in polyp tissues by flow cytometry. Recurrent CRSwNP patients exhibited higher levels of MDM3 compared to non-recurrent patients. This increase in MDM3 was positively correlated with the Lund-Mackay score, the number of infiltrated tissue eosinophils, and IL-5 expression levels. <em>Ex vivo</em> polarized alternatively activated (M2a) macrophage preferentially expressed MDM3 marker genes, which can be used as the substitute for MDM3 within the polyp tissues. M2a macrophages engulfed more <em>Staphylococcus aureus</em> than classically activated (M1) macrophages. However, interferon lambda 1 (IFN-λ1) did not alter the bacterial killing efficiency of M2a macrophages, nor did it affect the activation of reactive oxidase substrate (ROS) and signal transducer and activator of transcription 1 (STAT1) pathway and viability. The increase in MDM3 within polyp tissues, similar to classical M2a macrophages, acted as bacterial reservoirs and contributed to persistent inflammation, offering insights into the underlying mechanisms of CRSwNP.</div></div>","PeriodicalId":9795,"journal":{"name":"Cellular immunology","volume":"411 ","pages":"Article 104953"},"PeriodicalIF":3.7,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143834034","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":"Dexmedetomidine modulates peritoneal macrophage to attenuate lipopolysaccharide-induced inflammation","authors":"Tao Wang ,&nbsp;Rui Pan ,&nbsp;Jianli Wen ,&nbsp;Xinglong Ma","doi":"10.1016/j.cellimm.2025.104942","DOIUrl":"10.1016/j.cellimm.2025.104942","url":null,"abstract":"<div><h3>Purpose</h3><div>To investigate how Dexmedetomidine (Dex) modulates the function of peritoneal macrophages (PMs) to reduce lipopolysaccharide (LPS)-induced inflammation.</div></div><div><h3>Methods</h3><div>The anti-inflammatory effect of Dex on LPS-stimulated PMs was assessed by examining its impact on their proliferation, phagocytosis, and polarization. Proliferation and phagocytic activity were measured using CCK-8 and Neutral Red staining assays, respectively. The levels of inflammatory mediators were quantified using ELISA. Additionally, macrophage polarization was evaluated via ELISA, flow cytometry, and Western blot analysis to identify shifts in macrophage phenotypes.</div></div><div><h3>Results</h3><div>Dex increased the proliferation and phagocytic capabilities of PMs, thereby mitigating LPS-induced inflammation. It suppressed pro-inflammatory mediators, including tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), and high mobility group box 1 (HMGB1), while increasing levels of the anti-inflammatory cytokine interleukin-10 (IL-10). Furthermore, Dex promoted M2-type macrophage polarization, characterized by increased expression of IL-10, CD206, Arg-1, and CD11c. This effect was mediated through the JAK1/STAT6 signaling pathway, promoting M2 polarization, which was attenuated when JAK1 and STAT6 expression were downregulated.</div></div><div><h3>Conclusion</h3><div>Dex reduces LPS-induced inflammation in part by enhancing the proliferation, phagocytosis, and M2 polarization of PMs, with a key role for the JAK1/STAT6 pathway in promoting anti-inflammatory responses during sepsis.</div></div>","PeriodicalId":9795,"journal":{"name":"Cellular immunology","volume":"411 ","pages":"Article 104942"},"PeriodicalIF":3.7,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143619579","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}