European Journal of Immunology最新文献

{"title":"Mast Cell Phenotypic Heterogeneity Impacts the Interplay with Pathogenic Salmonella Typhimurium Bacteria","authors":"Christopher von Beek,&nbsp;Grisna I. Prensa,&nbsp;Julia H. M. Andersson,&nbsp;Gunnar Pejler,&nbsp;Mikael E. Sellin","doi":"10.1002/eji.70040","DOIUrl":"https://doi.org/10.1002/eji.70040","url":null,"abstract":"<p>Mast cells (MCs) lodge within barrier tissues and respond to infectious microbes. Recent work demonstrated that MCs differentiate their cytokine response to extracellular versus invasive Gram-negative enterobacteria by a two-step activation mechanism that integrates Toll-like-receptor (TLR) sensing with signals elicited by type-III-secretion-system (TTSS) effectors during bacterial invasion. However, multiple MC subtypes exist, and it remains unclear how their phenotypic heterogeneity impacts microbial interactions. We find that murine MCs maintained in IL-3, or differentiated toward a connective-tissue phenotype (CT-MCs), respond potently to the enteropathogen <i>Salmonella enterica</i> Typhimurium (<i>S</i>.Tm) through two-step activation, with the TLR component explained by functional TLR4 and TLR2. By contrast, murine mucosal mast cells (M-MCs) express insignificant levels of these TLRs, therefore being unresponsive to extracellular <i>S</i>.Tm, but still mounting a response to invasive bacteria. Following invasion, MC granule maintenance by serglycin restricts <i>S</i>.Tm vacuolar and cytosolic colonization. Notably, this has no impact on the cytokine release from infected MCs, thus uncoupling <i>S</i>.Tm´s intracellular life-cycle from the MC cytokine response. Finally, human LUVA MCs employ a variant of two-step activation where TLR2/6 signaling combines with the TTSS-elicited signals. Together, this study explains how MC subtypes can respond differently to <i>S</i>.Tm-infection depending on their TLR expression and granule features.</p>","PeriodicalId":165,"journal":{"name":"European Journal of Immunology","volume":"55 8","pages":""},"PeriodicalIF":3.7,"publicationDate":"2025-08-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/eji.70040","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144881121","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":"TLR9-Driven S-Palmitoylation in Dendritic Cells Reveals Immune and Metabolic Protein Targets","authors":"Juan N. Quiroz,&nbsp;Malte Sielaff,&nbsp;Daria Kondrateva,&nbsp;Fatima Boukhallouk,&nbsp;Gloria J. Godoy,&nbsp;Cecilia R. Molina,&nbsp;Brecht Moonen,&nbsp;Claudia C. Motran,&nbsp;Jeroen Bogie,&nbsp;Hugo D. Luján,&nbsp;Stefan Tenzer,&nbsp;Tim Sparwasser,&nbsp;Luciana Berod","doi":"10.1002/eji.70039","DOIUrl":"https://doi.org/10.1002/eji.70039","url":null,"abstract":"<p>Dendritic cells (DCs) rely on Toll-like receptor 9 (TLR9) to detect unmethylated CpG motifs in microbial DNA, triggering essential immune responses. While the downstream signaling pathways of TLR9 activation are well characterized, their impact on S-palmitoylation is unknown. S-palmitoylation, involving the reversible attachment of palmitic acid to cysteine residues, plays a crucial role in regulating protein function and is catalyzed by the ZDHHC family of palmitoyl-acyltransferases (PATs). In this study, we investigated the S-palmitoylated proteome of bone marrow-derived GM-CSF DCs (GM-DCs) at resting and following TLR9 activation with CpGB. Using the click-chemistry-compatible analog 17-octadecynoic acid (17-ODYA) and mass spectrometry (MS)-based proteomics, we characterized dynamic remodeling of S-palmitoylation in response to TLR9 activation. This included enrichment of targets involved in immune and metabolic pathways. Transcriptomic analysis of mice and human DCs revealed TLR9-driven modulation of PAT-encoding genes. Subsequently, we explored the contribution of <i>Zdhhc9</i> expression to the regulation of S-palmitoylation in DCs. Using gene knockout approaches, we identified candidate protein targets potentially linked to ZDHHC9 activity. Interestingly, modulation of <i>Zdhhc9</i> expression alone did not influence DC maturation, suggesting that other PATs might compensate for its activity. Together, our findings reveal a novel layer of regulation in TLR9 signaling mediated by S-palmitoylation.</p>","PeriodicalId":165,"journal":{"name":"European Journal of Immunology","volume":"55 8","pages":""},"PeriodicalIF":3.7,"publicationDate":"2025-08-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/eji.70039","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144869601","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":"Human T Cell Responses to Flavivirus Vaccines","authors":"David Wullimann,&nbsp;Hans-Gustaf Ljunggren","doi":"10.1002/eji.70027","DOIUrl":"https://doi.org/10.1002/eji.70027","url":null,"abstract":"<p>Flaviviruses are major human pathogens that continue to pose a global health threat, and vaccination is an effective strategy to protect against disease from several flaviviruses. Flavivirus vaccines are believed to confer protection primarily through antibody responses; however, the role of T cells in vaccine immunity remains less explored despite demonstrated contribution in the response to natural infection. This review examines T cell responses induced by licensed or developing flavivirus vaccines, their contribution to protection, and key findings highlighting the importance of cellular immunity. We discuss the role of memory T cells, including CD4+ and CD8+ subsets, in flavivirus vaccine-induced immunity and compare the immunogenicity of live attenuated versus inactivated vaccines. We also discuss the significance of T cell immunity, cross-reactivity, and vaccine platform design in shaping durable and broad protection. Additionally, we broaden the discussion toward other human RNA viruses, including the influenza virus and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). A better understanding of the role of T cell immunity will be essential for optimizing the use of current flavivirus vaccines and developing next-generation approaches capable of providing long-lasting immunity against emerging and re-emerging flavivirus threats.</p>","PeriodicalId":165,"journal":{"name":"European Journal of Immunology","volume":"55 8","pages":""},"PeriodicalIF":3.7,"publicationDate":"2025-08-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/eji.70027","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144861933","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":"BMP Signaling Alleviates Allergic Airway Inflammation by Controlling Group 2 Innate Lymphoid Cells Homeostasis","authors":"Shan Yue,&nbsp;Huihui Li,&nbsp;Zhiqiang Yan,&nbsp;Mengying Xie,&nbsp;Mengyuan Dai,&nbsp;Mingying Zhang,&nbsp;Wei Xu","doi":"10.1002/eji.70038","DOIUrl":"https://doi.org/10.1002/eji.70038","url":null,"abstract":"<div>\u0000 \u0000 <p>Recent studies have highlighted the important role of bone morphogenetic proteins (BMPs) in immunoregulation. Our earlier work identified the expression of BMP receptors on lymphoid progenitors and group 2 innate lymphoid cells (ILC2s) in the bone marrow. However, the precise function of BMP signaling in the development and activity of ILC2s remains unclear. This study aimed to investigate whether BMP signaling regulates the generation of ILC2s and their effector functions during lung airway inflammation. We generated BMP receptor 2 (BMPR2) conditional knockout (CKO) mice to analyze ILC2 development and function. We found that BMPR2 deficiency led to an increased number of ILC2s in the lung at steady state, primarily due to enhanced cell proliferation. This expansion resulted in aggravation of early type 2 response in a papain-induced allergic airway inflammation model. BMP4 restrained the proliferation of ILC2s in vitro and in vivo through activation of the canonical BMP signaling pathway. Administration of BMP4 alleviated papain-induced airway inflammation in control mice, whereas this therapeutic effect was abolished in BMPR2 conditional knockout mice. In conclusion, our study demonstrated that BMP signaling regulates allergic airway inflammation by controlling ILC2s homeostasis.</p>\u0000 </div>","PeriodicalId":165,"journal":{"name":"European Journal of Immunology","volume":"55 8","pages":""},"PeriodicalIF":3.7,"publicationDate":"2025-08-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144861935","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Booster Injection with Birch Pollen Extract Activates B-Cellular Memory Responses in Patients Having Completed Allergen Immunotherapy","authors":"Carolin Baum,&nbsp;Christian Möbs,&nbsp;Wolfgang Pfützner","doi":"10.1002/eji.70034","DOIUrl":"https://doi.org/10.1002/eji.70034","url":null,"abstract":"<p>Allergen immunotherapy (AIT) of patients with IgE-mediated allergy results in the synthesis of blocking IgG antibodies mediating allergen tolerance. However, as antibody concentrations wane after stopping AIT, tolerance may be lost. The impact of a single booster allergen application on B-cellular memory in AIT-treated birch pollen (BP)-allergic patients was investigated. Twenty-five patients with BP allergy who finished AIT 3–12 years ago received one allergen injection approximately 4 months prior to the next BP season. We determined peripheral Bet v 1-specific IgG-secreting cells (ASC) by ELISPOT analysis and BP-specific IgG, IgG4, and IgE serum antibodies by ImmunoCAP, and the allergen-blocking capacity of IgG/IgG4 antibodies by ELIFAB assay. Clinical responses were assessed by visual analog scales. Immunological findings were compared with the primary B cell response of 12 BP-allergic patients receiving conventional AIT. Bet v 1-specific ASC significantly increased 2–4 weeks after BP-injection, accompanied by enhanced levels of both BP-specific IgG/IgG4 antibodies and allergen-blocking serum activity. Compared with conventional up-dosing, a single booster vaccination led to a markedly stronger B cell response after 4 weeks. Allergen booster injection activates B-cellular memory associated with blocking IgG/IgG4 antibodies, pointing to reinforcement of allergen tolerance after completion of AIT.</p>","PeriodicalId":165,"journal":{"name":"European Journal of Immunology","volume":"55 8","pages":""},"PeriodicalIF":3.7,"publicationDate":"2025-08-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/eji.70034","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144861934","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":"Mast Cells Are Not Essential for Pubertal Mammary Gland Branching","authors":"Simran Kapoor,&nbsp;Clara M. Munz,&nbsp;Jimmy Marsden,&nbsp;Cyril Carvalho,&nbsp;Holly Tinsley,&nbsp;Marlene Magalhaes Pinto,&nbsp;Bert Malengier-Devlies,&nbsp;Solvig Becker,&nbsp;Guillaume Seuzaret,&nbsp;Katelyn Patatsos,&nbsp;Ramazan Akyol,&nbsp;Amy B. Pederson,&nbsp;Gillian Wilson,&nbsp;Marc Dalod,&nbsp;Rebecca Gentek","doi":"10.1002/eji.70036","DOIUrl":"https://doi.org/10.1002/eji.70036","url":null,"abstract":"<p>Mast cells are long-lived, tissue-resident immune cells of the myeloid lineage with cardinal functions in allergy and atopic disease. They are now increasingly recognized also for protective roles, for example against infections and venoms. Other functions originally assigned to mast cells in development and physiology, however, have been refuted, and for yet others, the true contribution of mast cells remains uncertain. Mast cells have been implicated in promoting ductal branching in the pubertal mammary gland, the organ that produces and secretes milk in mammals, but these findings are based on mouse models that are not mast cell-specific. In this study, we therefore re-addressed the impact of mast cells on mammary gland branching using several complementary genetic models, including a newly generated transgenic mouse line (<i>Ms4a2</i>^lsl-hDTR). We report that neither constitutive deficiency of mast cells, nor their conditional ablation induced at puberty affects mammary gland branching. Our results thus dispute that mast cells promote this process in mice, at least in a unique and non-redundant manner. This study adds to a growing body of work clarifying the biological roles of mast cells and further expands the toolbox available to the field of mast cell research.</p>","PeriodicalId":165,"journal":{"name":"European Journal of Immunology","volume":"55 8","pages":""},"PeriodicalIF":3.7,"publicationDate":"2025-08-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/eji.70036","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144861936","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 Streptomyces Metabolite Thiostrepton Inhibits Regulatory T Cell Differentiation and Function to Boost Antitumor Immune Responses","authors":"Luana Silva,&nbsp;Luís Almeida,&nbsp;Fatima Al-Naimi,&nbsp;Daniele Carvalho Nascimento,&nbsp;Aleksandra Lopez Krol,&nbsp;Luis Eduardo Alves Damasceno,&nbsp;Hakim Echchannaoui,&nbsp;José Carlos Alves-Filho,&nbsp;Luciana Berod,&nbsp;Tim Sparwasser","doi":"10.1002/eji.70035","DOIUrl":"https://doi.org/10.1002/eji.70035","url":null,"abstract":"<p>Regulatory T cells (Tregs) are associated with enhanced tumor progression and reduced therapy response rates. Therefore, overcoming the Treg-mediated immunosuppressive barrier within the tumor to enhance antitumor immune responses is of central interest to advance cancer immunotherapy. To date, no tools exist that can be exploited to dampen Treg function and differentiation in vivo. Here, we show for the first time that the antibiotic thiostrepton exerts a potent inhibitory effect on Tregs. Mechanistically, thiostrepton disrupts Treg differentiation, reduces the expression of Treg activation markers, and inhibits Treg suppressive functions. Accordingly, using an MC38 tumor model, we demonstrate that thiostrepton treatment reduces the number of intratumoral Foxp3⁺ Treg cells and prevents tumor growth. These effects are conserved in human T cells, as thiostrepton also inhibits the differentiation of human Tregs. Our findings highlight thiostrepton as a promising Treg-targeting immunomodulatory compound with the potential to enhance antitumor immune responses.</p>","PeriodicalId":165,"journal":{"name":"European Journal of Immunology","volume":"55 8","pages":""},"PeriodicalIF":3.7,"publicationDate":"2025-08-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/eji.70035","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144861932","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":"Neuro-ILC Interactions in Host Physiology and Defence","authors":"Cristina Godinho-Silva,&nbsp;Miguel Rendas,&nbsp;Henrique Veiga-Fernandes","doi":"10.1002/eji.70037","DOIUrl":"https://doi.org/10.1002/eji.70037","url":null,"abstract":"<p>Over the past decade, innate lymphoid cells (ILCs) have emerged as key partners of neuroimmune interactions. Bidirectional interactions between ILCs and the peripheral nervous system regulate mucosal barrier homeostasis, inflammation, and defence. Recent findings indicated that neuro-ILC circuits also operate in the liver, adipose tissue, skin, and systemically, regulating a wide range of physiological processes. Notably, brain regions and peripheral neural circuits were shown to regulate tissue neuro-ILC interactions, shedding light on immunoregulatory brain–body axes. Here, we review recent insights into tissue, organ, and systemic neuro-ILC circuits. We highlight neuroimmune brain–body and inter-organ communication axes integrating external environmental cues and internal body states to coordinate host physiology. Finally, we discuss how these recent findings are positioning neuro-ILC circuits at the centre stage of body physiology and defence, with profound implications in the understanding of health and disease.</p>","PeriodicalId":165,"journal":{"name":"European Journal of Immunology","volume":"55 8","pages":""},"PeriodicalIF":3.7,"publicationDate":"2025-08-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/eji.70037","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144814677","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 Mitigating Effect of Combined Glucocorticoids with Immune Checkpoint Inhibitors on Lymphocyte Activation Gene-3 and Programmed Death-1 Expression","authors":"Smadar Gertel,&nbsp;Ari Polachek,&nbsp;Victoria Furer,&nbsp;Tali Ofir Dovrat,&nbsp;Chen Avaky,&nbsp;Adi Broyde,&nbsp;Hila Nochimovitz,&nbsp;Ori Elkayam","doi":"10.1002/eji.70033","DOIUrl":"https://doi.org/10.1002/eji.70033","url":null,"abstract":"<p>Cancer immunotherapy with immune checkpoint inhibitors (ICI) shows promising therapeutic efficacy but can cause immune-related adverse events (irAEs). Glucocorticoids (GCs) are commonly employed with ICI to mitigate irAEs. We had found previously that GCs upregulate significantly the inhibitory molecule, lymphocyte activation gene-3 (LAG-3) in peripheral blood and synovial fluid mononuclear cells (PBMCs and SFMCs, respectively). Here, we investigated the effect of GCs combined with ICI on LAG-3 and programmed death-1 (PD-1) expression in SFMCs of 32 inflammatory arthritis patients and PBMCs of 15 healthy controls. GC+Pembrolizumab (PEM, anti-PD-1) induced IL-10 and suppressed IFN-γ, TNF-α, and IL-17A mRNA expressions compared with PEM alone in PBMCs and SFMCs. PBMC proliferation was markedly inhibited by GC+PEM (3.5 ± 0.7%, <i>p </i>&lt; 0.0006) compared with PEM alone (26.2 ± 6.5%). GC+PEM increased the CD4⁺LAG-3⁺ T cells (4.9±1.2%, <i>p </i>&lt; 0.03) compared with PEM alone (0.9 ± 0.3%), but did not affect CD4⁺PD-1⁺ T cells. The effect of the drugs on synovial cells revealed that GC+PEM remarkably increased the CD14⁺LAG-3⁺ cells in SFMCs (10.4 ± 2.0%, <i>p </i>&lt; 0.0001) compared with PEM alone (0.6 ± 0.2%), but not the CD14⁺PD-1⁺ cells. Thus, GC combined with ICI might exhibit contrasting activity via upregulation of CD4⁺LAG-3⁺ T and CD14⁺LAG-3⁺ cells in circulation and synovial milieu, respectively, possibly interfering with the ICI activity.</p>","PeriodicalId":165,"journal":{"name":"European Journal of Immunology","volume":"55 8","pages":""},"PeriodicalIF":3.7,"publicationDate":"2025-08-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/eji.70033","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144814676","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":"A Collaborative Special Issue: Highlights from the Belgian–Dutch Immunology Meeting","authors":"Melissa M. J. van Gool,&nbsp;Hind Hussein,&nbsp;Anissa Zouzaf,&nbsp;Farahnaz Rayatdoost","doi":"10.1002/eji.70030","DOIUrl":"https://doi.org/10.1002/eji.70030","url":null,"abstract":"<p>On November 21–22, 2023, the third Joint Belgian–Dutch Immunology Meeting took place at the Flanders Meeting &amp; Convention Center in Antwerp, Belgium. This event brought together over 700 researchers and clinicians from across the Netherlands and Belgium to exchange the latest insights in fundamental and translational immunology. Co-organized by the Belgian Immunological Society (BIS) and the Dutch Society for Immunology (NVVI), the meeting featured keynote lectures from international leaders in the field, including Prof. Manfred Kopf, Prof. Donna Farber, Dr. Julie Déchanet-Merville, and Prof. Georg Schett. The scientific program also included thematic parallel sessions with selected abstract presentations, poster sessions, and a dedicated Young Investigators session to highlight the work of early-career scientists. Building on the legacy of previous joint BIS–NVVI meetings held in 1988 and 2002, the 2023 edition marked a renewed commitment to cross-border collaboration and the exchange of scientific ideas between the Belgian and Dutch immunology communities.</p><p>The Belgian–Dutch Immunology Highlights special issue, inspired by the 2023 Joint Belgian–Dutch Immunology Meeting, features 20 selected original research and review articles, reflecting the scientific diversity and depth of topics presented at the meeting from fundamental insights into infection and inflammation to advances in immune regulation and emerging therapeutic strategies. Among these, we especially highlight seven articles from first-time authors: five by first-time first authors and two by first-time corresponding authors. For many of them, this marks an important milestone in their scientific careers.</p><p>Innate immune responses are not only regulated by external cues but are also modulated by sophisticated internal systems, which ensure an adequate balance between activation and suppression to preserve systemic homeostasis as well as tissue integrity.</p><p>Koops &amp; Meyaard [<span>1</span>] review a lesser-known yet crucial inhibitory checkpoint in myeloid cells: the inhibitory receptor VSTM1/SIRL-1. As a pattern recognition receptor with an inhibitory function, VSTM1 suppresses the production of reactive oxygen species (ROS) and the formation of neutrophil extracellular traps (NETs) in response to both host and microbial ligands, including LL37, S100, and bacterial phenol-soluble modulins (PSMs). Its function highlights the importance of active immune dampening mechanisms, especially in contexts where the presence of pathogens does not necessitate the involvement of immune cells, such as in the skin and gut.</p><p>Parallel to this, Biscu et al. [<span>2</span>] illustrate how environmental cues, including dietary inputs such as vitamins and iron, microbial metabolites, and local tissue factors, shape macrophage function via metabolic rewiring. This plasticity supports both inflammatory and reparative programs and is central to the concept of macrophage niches. ","PeriodicalId":165,"journal":{"name":"European Journal of Immunology","volume":"55 8","pages":""},"PeriodicalIF":3.7,"publicationDate":"2025-08-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/eji.70030","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144810978","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}