Maternal immune activation triggers elevated cytokines (IL-6 and IL-17A), disrupting fetal immune system development. This not only alters hematopoietic stem cell balance but also leads to ILC2 hyperactivation in the lung, which could potentially affect susceptibility to allergic diseases in the offspring. ABSTRACT Maternal immune activation (MIA) refers to an immune response triggered in a … Read more
Recent evidence supports a model in which the pool of adult immune cells is actually composed of cells derived from fetal, neonatal, and adult waves of hematopoiesis. In this review, we discuss this evidence in the context of innate lymphoid cells (ILC), with a focus on the environmental signals required for their development during early … Read more
Our study shows that mature B cells expressing IgD exhibit significantly higher sensitivity to glucocorticoid (GC)-induced cell death. This elevated sensitivity is specifically dependent on GC receptor (GR) expression and is accompanied by enhanced activation as well as terminal differentiation of B cells. Our findings elucidate how exogenous GCs affect B cell survival and suggest … Read more
The tissue metabolic environment in autoimmunity influences immune and nonimmune cells via fuelling cellular metabolism or through metabolic signalling. Intracellular metabolic sensors combine several environmental cues to control transcription, metabolism, and cell function. The function of each cell contributes to the concerted dysfunctional behaviour of a tissue in autoimmunity. ABSTRACT Autoimmunity causes damage to organs … Read more
This review examines the failure of peripheral immune tolerance as the initiating factor in rheumatoid arthritis (RA), focusing on the role of dendritic cells. It discusses strategies to convert these cells from immunogenic to tolerogenic states, while also exploring emerging research on the anatomical sites where this critical loss of tolerance occurs. ABSTRACT Rheumatoid arthritis … Read more
We report the case of a stage 4 mantle cell lymphoma patient, resistant to conventional first- and second-line therapies, treated with CAR-T cells. The therapy was initially efficacious, with an appreciable CAR-T cells expansion in vivo. However, downregulation of CD19 expression on malignant B cells led to sudden therapy failure.
Loss of the casein kinase 1 scaffolding protein FAM83H compromises bone marrow lymphopoiesis, reduces Foxn1 expression in cortical thymic epithelial cells (TEC), disrupts thymic architecture and TEC identity, and ultimately impairs double-negative thymocyte proliferation and T-cell production. ABSTRACT Family of Sequence Similarity 83H (FAM83H/SACK1H) is primarily expressed in epithelial cells, where it interacts with casein … Read more
The MHC-E peptide binding methods described here—nano-differential scanning fluorimetry and fluorescence polarisation—demonstrate shared peptide binding repertoires with subtle binding hierarchy differences for the tested HLA-E and Mamu-E allotypes. When combined, these methods illustrate how minor MHC-E-peptide thermal stability changes equate to significant binding strength differences. ABSTRACT The primary function of MHC-E—human leukocyte antigen (HLA)-E in … Read more
The increased lactate secretion by B cells from people with obesity and aging is a stimulus for pathogenic autoimmune anti-dsDNA antibodies. The effects of lactate are mediated by phosphorylated signal transducer and activator of transcription 3 (p-STAT3) and inhibited by a neutralizing antibody that blocks the lactate transporter SLC5A12, responsible for lactate uptake and activation … Read more
Picture-book compartmentalization makes tonsillar tissue an ideal model to study spatial immunology. Using single-molecule imaging (SMI) of whole-tissue sections, we showcase many an alternative view on tissue composition and architecture that these data and concomitant analyses provide—at the level of single cells, cellular neighborhoods, and anatomical units such as germinal centers and epithelial substructures. ABSTRACT The … Read more
SARS-CoV-2 mRNA vaccination triggers bystander activation of B cells, transiently increasing antibody levels after the first vaccination against influenza, RSV, and tetanus. Reactivation of B cell responses also occurred, where (CD11c+) MBC and DN3 are expanded after SARS-CoV-2 mRNA vaccination, independent of antigen exposure. ABSTRACT After antigen encounter, long-lived antibody-secreting cells (ASC) secrete high-affinity circulating … Read more
Synovial tissue macrophages are essential coordinators of joint homeostasis and inflammatory responses in rheumatoid arthritis. Here, we highlight recent advances that have enabled a deeper characterization of synovial tissue macrophages and their distinct phenotypes and functions in health and disease. ABSTRACT Synovial tissue macrophages are critical orchestrators in the pathogenesis of rheumatoid arthritis, comprising a … Read more
Our cover features images related to flow cytometry techniques widely used for analysis of function and phenotypes of major human and murine immune cell subsets, superimposed on a multidimensional immune cell population scatter plot. These images are taken from the third edition of EJI’s Flow Cytometry Guidelines by Cossarizza et al., a comprehensive resource prepared … Read more
The C-terminal of TSP-1 senses cell contact, which triggers N-terminal cleavage by urokinase, adhesion, and cytoplasmic spreading in T cells and platelets. In contrast, full-length TSP-1 induces the development of polar cell shape and migration in T cells 2D and 3D; polar cell shape 2D, independent of its receptor LRP1, and polar cell shape 3D … Read more
This review summarizes emerging spatially resolved multi-omics approaches revealing organized cell–cell interactions in skeletal muscle and brain inflammation. These tools uncover radiating molecular programs and niche-specific immunopathology that shape cellular reactivity and vulnerability. ABSTRACT Spatial omics technologies enable high-resolution mapping of transcriptomic, proteomic, and metabolic profiles within intact tissues, revealing how immune, stromal, and parenchymal … Read more
CCR7-mediated chemokine signaling regulates the medullary migration of thymocytes to establish self-tolerance. By comparing the thymic phenotype of Ccl21b-KO mice with that of Ccl21a-KO mice, we show that Ccl21a plays a predominant role compared with Ccl21b among CCR7 ligands in the thymus. ABSTRACT Self-tolerance in T cells is a vital self-defense strategy for mammals to … Read more
HLDA Workshops were established 40 years ago to develop a standardized CD molecule nomenclature for leukocyte cell-surface molecules by comparing monoclonal antibodies (mAbs) produced by different laboratories and companies. The HLDA11 Workshop focused on validating G-protein-coupled receptors (GPCRs) targeting mAbs and assessing cell-type-specific expression patterns in leukocytes. ABSTRACT Monoclonal antibodies (mAbs) targeting cell-surface molecules are … Read more
The RNA-binding ROQUIN paralogs are critical immune regulators. We demonstrate that mast cell-specific deficiency for ROQUIN-1 and ROQUIN-2 in mice leads to loss of mast cells in serous cavities. ROQUIN-1 and 2 ablation does not affect mast cell degranulation or proinflammatory cytokine secretion, although they regulate many mRNAs directly or indirectly. ABSTRACT Mast cells are … Read more
SARS-CoV-2 vaccination in rheumatoid arthritis leads to the development of CD4+ and CD8+ spike-specific T cell memory, regardless of immunosuppressive therapies, and the number of vaccine injections. CD4−CD8− double-negative (DN) T cells responded to SARS-CoV-2 peptide epitopes and differentiated into CD8+ cytotoxic T cells after stimulation, suggesting a role in exacerbating the inflammation in RA … Read more
Antibody feedback dynamically shapes the selective landscape for GC B-cells, acting as a driving force of Darwinian-like affinity maturation of B-cell receptors (A). It also balances epitope usage, leading to equal competition among B cell clones specific for different epitopes and allowing the emergence of clones specific for new epitopes (B). ABSTRACT Antibody feedback in … Read more
Early B cell activation requires both FcµR and IgM-mediated complement signaling, which together drive initial clonal expansion, class-switch recombination, germinal center (GC) entry, and plasma cell differentiation. During the GC reaction, IgM BCR-mediated complement activation, but not FcµR, supports GC B cell survival, proliferation, and affinity maturation. ABSTRACT Secretory IgM plays a pivotal role in … Read more
Murine allergy model outcomes differ by sensitization route, allergen type, and mouse strain, influencing mechanisms such as IgE and mast cell involvement and the therapeutic relevance of each model. Understanding how experimental parameters shape outcomes is essential for selecting appropriate models and effectively translating findings to clinical applications. ABSTRACT Immunoglobulin E (IgE)–mediated immediate hypersensitivity reactions … Read more
Staphylococcal enterotoxin A (SEA) alters monocyte differentiation and function, while preserving T cell stimulatory capacity. SEA-primed macrophages downregulate antigen-presenting markers yet drive heightened T-cell proliferation and IFN-γ secretion. These findings reveal mechanisms of SEA-mediated immune modulation and superantigen-driven inflammation. ABSTRACT Staphylococcal enterotoxins (SE) crosslink the MHC-II on antigen-presenting cells (APC) with the T-cell receptor, inducing … Read more
Severe COVID-19 is associated with hyperinflammation driven by anti-spike IgG immune complexes (ICs) contributing to macrophage hyperactivation, thrombosis, and tissue damage. This study shows that anti-spike IgG ICs induce rapid metabolic reprogramming, specifically glycolysis, fatty acid synthesis, and the pentose phosphate pathway, which is essential for the inflammatory response. Targeting these metabolic pathways may offer … Read more
Unannotated splicing and translation of non-canonical open reading frames generate a diverse repertoire of cryptic proteins. Most are rapidly degraded, rendering them possible MHC-I substrates. Yet, a subpopulation can adopt stable structures and impart advantageous functions. This dichotomy both expands the antigen landscape and provides a framework for protein evolution. ABSTRACT The widespread translation of … Read more
This is an update to the Guidelines for the use of flow cytometry and cell sorting in immunological studies (third edition), Chapter 3: 12C, by Cossarizza et al. Administration of anti-ARTC2 nanobody(S+16a) prevents cell death during tissue processing. We demonstrate that the phenotype of CD44midTreg is significantly impacted, whereas the eTreg phenotype remains stable following … Read more
Here, we show increased MHC class I levels on B cells, classical and intermediate monocytes, and a shift in CD8+ T cells toward a Tc1-skewed, proinflammatory phenotype in the peripheral blood mononuclear cells of people with type 2 diabetes mellitus. ABSTRACT Effective antigen presentation by major histocompatibility complex (MHC) molecules to T cells is crucial … Read more
HCV re-infection is common after spontaneous clearance of the initial infection. In the rare group of super-clearers who clear repeatedly, HCV-specific CD8+ T memory stem cells (TSCM) retain stemness, proliferation, and multipotency, sustaining immune protection. In contrast, clearer chronics lose these properties. TSCM self-renewal underpins durable immunity and should inform vaccine design. ABSTRACT Natural clearance … Read more
Selecting a sensitive test system is crucial to measure IFNα in serum samples. Simoa digital ELISA stands out for its high sensitivity and strong correlation with transcript-based IFN-induced gene (ISG) scores. In SLE, the ISG score is explained by circulating IFNα levels with negligible contribution from IFNβ or IFNγ. Created in BioRender.
Using mass cytometry, we map the heterogeneous activation of the STING pathway at single-cell resolution in cell lines and primary human immune cells and validate them with conventional techniques. ABSTRACT The stimulator of interferon genes (STING) pathway plays a pivotal role in innate immunity, acting as a key sensor of cytosolic DNA to initiate type-I … Read more
We optimised a protocol for mHA-specific Treg (mTreg) selection in an HLA-matched context while defining its phenotype, transcriptional state and function. mTreg were highly activated and exerted specific, HLA class II-, contact-dependent suppression. This protocol can be explored as a highly personalised antigen-specific Treg-based therapy in future clinical trials for cGVHD. ABSTRACT Graft-versus-host disease is … Read more
This review highlights the hierarchical transcriptional networks that govern macrophage specification and function. We describe how lineage-determining, identity-imprinting, and tissue-specific transcription factors coordinate macrophage differentiation and specialization across organs, emphasizing the transcriptional regulation underlying macrophage diversity in health and disease. ABSTRACT Tissue-resident and recruited macrophages are integral to organ development, homeostasis, immunity, and disease pathogenesis. … Read more
The Janus face of group 3 innate lymphoid cells (ILC3s). ILC3s are highly plastic and can adapt their immunoregulatory roles according to the local context, balancing tolerance and activation. Influenced by tissue-specific environmental cues, they can express MHC class II molecules either alone or jointly with costimulatory molecules, therefore presenting acquired antigens for controlling or … Read more
Our cover features images related to flow cytometry techniques widely used for analysis of function and phenotypes of major human and murine immune cell subsets, superimposed on a multidimensional immune cell population scatter plot. These images are taken from the third edition of EJI’s Flow Cytometry Guidelines by Cossarizza et al., a comprehensive resource prepared … Read more
How the immune system of people with diabetes responds to vaccination against respiratory viruses is not well understood. Using activation-induced markers to identify, quantify, and functionally characterize Spike-specific CD4+ and CD8+ T cells after SARS-CoV-2 vaccination, we show defects in T cell memory maintenance and an IL-10 and IL-13-dominated T cell response in people with … Read more
This review highlights recent advances that enable spatially resolved analysis of immunometabolism within tissue microenvironments. Integrating mass spectrometry imaging, vibrational microscopy, and spatial omics reveals how metabolic organization shapes immune function in cancer and other pathologies. ABSTRACT The metabolic programs of immune cells influence their activation, differentiation, and effector functions. While much of immunometabolism has … Read more
How chronic immune stimulations differentially shape CD4⁺ T cell senescence remains unclear. Using high-dimensional mass cytometry and functional profiling, we show that cytomegalovirus (CMV) drives expansion of cytotoxic CD27−CD28− CD4⁺ T cells, whereas rheumatoid arthritis (RA) exerts nonredundant effects by modulating their effector capacity. ABSTRACT Chronic antigen exposure drives CD4⁺ T cell senescence, yet how … Read more
Fibroblastic reticular cells (FRCs) in lymph nodes contribute to peripheral tolerance via MHC-class-II-mediated antigen presentation. Using scRNAseq and protein analysis, we identify BST1+CD200+ FRCs, including the mature T cell-zone FRCs, as key MHC-class-II expressing subsets in mice and humans, highlighting their potential role in immune regulation. ABSTRACT Autoimmunity can be initiated by autoreactive T cells … Read more
CD8+CD69− memory T cells (Schneider Revueltas et al.) were identified to reside in bone marrow besides canonical CD8+CD69+ tissue-resident memory T cells (TRM). In addition, CD4+CD69+ Tr1-like cells (Pulvirenti et al.) were preferentially found in bone marrow. Together, these findings illustrate diversity in the T cell subsets that reside long-term within the bone marrow. ABSTRACT Recent studies … Read more
Proposed mechanism underlying the repression of ZFP36 and induction of ZFP36L1 by calcineurin. ELK-1 is activated by stimuli and promotes the transcription of Zfp36. Calcineurin dephosphorylates active ELK-1 to inhibit its positive effect on Zfp36 transcription, while promoting NFAT-mediated Zfp36l1 transcription. ABSTRACT CD8+ T cells target infected or malignant cells via the production of pro-inflammatory … Read more
Prostaglandin E2 (PGE2) signaling through E-prostanoid receptors (EP) 2 and 4 induces a distinct human macrophage phenotype and affects their functions. Targeting the PGE2-EP2/4 axis in macrophages with soluble or nanoparticle-encapsulated EP2/4 antagonists counteracts the PGE2-induced effect in a 2D and 3D tumor microenvironment using patient-derived tumor organoids. ABSTRACT Prostaglandin E2 (PGE2) is one important … Read more
Innate lymphoid cells (ILCs) have emerged as critical regulators of immune defense, tissue repair, and metabolic homeostasis. By integrating environmental cues, they orchestrate tissue-specific metabolic adaptation. This review discusses ILC functions in adult energy regulation and proposes that neonatal ILCs play essential roles in postnatal metabolic and tissue maturation. ABSTRACT In the almost two decades … Read more
Our cover features images related to flow cytometry techniques widely used for analysis of function and phenotypes of major human and murine immune cell subsets, superimposed on a multidimensional immune cell population scatter plot. These images are taken from the third edition of EJI’s Flow Cytometry Guidelines by Cossarizza et al., a comprehensive resource prepared … Read more
Differentially methylated regions (DMRs) within the ZEB2 locus progressively demethylate during CD4+ and CD8+ T cell differentiation into cytotoxic CD4+ and CD8+ TEMRA subsets, respectively. This epigenetic remodeling tightly correlates with elevated ZEB2 expression, and ZEB2 knockout (KO) impairs the effector and cytotoxic function of CD4+ and CD8+ T cells. ABSTRACT Zinc finger E-box binding … Read more
In this article, the authors elucidated the immunoregulatory role of an oligonucleotide (ssON) that favors the induction of human tolerogenic dendritic cells (DC). The tolerogenic profile was evidenced by reduced responsiveness to lipopolysaccharides (LPS) (A). Importantly, the tolerogenic DCs had upregulated PD-L1 molecules and functionally inhibited the proliferation of alloreactive T cells and induced FoxP3+ … Read more
Neonatal mice infected with C. parvum and treated with MDP, a NOD2 agonist, exhibited reduced intestinal infection. This protective effect was mediated by a local immune response involving neutrophil recruitment, IL-22 production, antimicrobial peptide expression, and epithelial regeneration in an IFN-γ-dependent manner. Therefore, MDP administration enhances host defense mechanisms against C. parvum infection in neonatal … Read more
Primary immunodeficiency is a monogenic disorder that affects proper immune functioning. Diagnostic yield of these inherited diseases are burdened by the presence of variants of unknown significance. In this study we functionally validated novel variants associated with immunodeficiency to ascertain its pathogenicity. ABSTRACT Primary immunodeficiency diseases (PIDs) are inherited disorders caused by genetic defects affecting … Read more
Ligation of the activating LILRA5 receptor specifically stimulates ROS production by monocytes and neutrophils. Though LILRA5 transcripts are upregulated upon immune stimulation, surface LILRA5 expressions are dynamically regulated. Enhanced soluble LILRA5 was observed during immune challenge, suggesting that dynamic regulation of LILRA5 modulates ROS induction and innate immune responses. ABSTRACT Activating immune receptors provides mechanisms … Read more
NK cells kill tumor targets via antibody-dependent cellular cytotoxicity (ADCC), mediated by the receptor CD16A. We show that the bispecific innate cell engager acimtamig (AFM13) enhances ADCC and boosts NK cell serial killing. Live-cell imaging revealed that CD16A shedding is essential for efficient NK cell detachment and sustained killing. ABSTRACT Natural killer (NK) cells can … Read more
We show that sodium butyrate suppresses Tfh-cell differentiation, via HDAC inhibition, leading to inefficient germinal center responses and impaired antibody generation. This suboptimal humoral immunity fails to confer protection against virus infection, underscoring sodium butyrate’s potential impact on shaping GC-derived protective immunity. ABSTRACT The gut microbiome and its metabolites are critical regulators of intestinal homeostasis, … Read more
This review discusses the principles underlying the interplay of epigenetics, metabolism, and post-transcriptional regulation of gene expression mediated by RNA-binding proteins, both in the nucleus and in the cytoplasm. Particularly, it focuses on the relevance that these circuits have in lymphocytes and autoimmunity. ABSTRACT Changes in transcript abundance and isoforms, mediated by epigenetic and post-transcriptional … Read more
Th17 cells confer protection against Candida albicans infection. In patients with STAT1 gain-of-function (GOF) mutations and chronic mucocutaneous candidiasis (CMC), Candida-specific Th cell responses are numerically preserved but skewed toward Th1 and Th2. In a mouse model of mucosal vaginal infection, Th1 and Th2 cells fail to control fungal growth, and Th2 cells can even … Read more
Mice with inactivated PI3Kδ develop colitis, reminiscent of immune-related adverse effects observed in human patients treated with PI3Kδ inhibitors. We demonstrate that loss of PI3Kδ activity abrogates the Helios− peripherally induced Treg (pTreg) population in the mouse colon, resulting in inflammation and tissue damage that Helios+ thymic Tregs fail to control. ABSTRACT Peripherally derived regulatory T … Read more
Anti-SARS-CoV-2 spike IgA drives inflammation in human macrophages through FcαRI-Syk signaling. IgA2 immune complexes amplify cytokine production and alter glycolysis and mitochondrial function more potently than IgA1, indicating subclass-specific immunometabolic reprogramming. These findings identify IgA2 as a pathogenic factor in severe COVID-19 and highlight pathways with potential therapeutic relevance. ABSTRACT Severe COVID-19 is an immunological … Read more
Immune regulation is fundamentally spatial, shaped by tissue architecture and local cues. Spatial omics—transcriptomic, proteomic, metabolomic, lipidomic, and phosphoproteomic platforms—preserve coordinates while capturing high-dimensional data, revealing region-specific programs and niches. This review surveys key methods and applications in the intestine, lymphoid organs, and liver. ABSTRACT The immune system is deeply shaped by its anatomical context, … Read more
Purine Metabolism and Treg Stability. Nuermous enzymes (colored boxes) facilitate the conversion of ATP into AMP, ADO, IMP, inosine, and hypoxanthine. Purine metabolites can be recycled through the purine salvage pathway or undergo degradation to form uric acid, or be transported to the extracellualr environment. The pertubation of purine pathways can lead to significant changes … Read more
Using imaging mass cytometry (IMC), we spatially profiled Peyer’s patches and lymphoid follicles in IBD. In colonic Crohn’s disease, follicles showed enriched activated CD8⁺ T cells and B–T neighbourhoods—most pronounced in small B-cell patches—whereas ileitis resembled healthy tissue. Spatial features outperformed simple cell-frequency readouts. ABSTRACT Lymphoid follicles in the human gut are critical immune hubs, … Read more
Analysis of BALF and blood of asthmatic horses revealed local and systemic immunological variations related to NET formation and cholesterol homeostasis. Higher NET formation, lower cellular cholesterol and dysregulated NET regulators (e.g., eCATH, DNase, ANCAs) were associated with clinical disease severity. These results provide novel mechanistic insights into EA pathogenesis. ABSTRACT Equine asthma (EA) is … Read more
Recent clinical trials highlight the potential of antigen-specific tolerance therapies in autoimmune disease. Building on this, next-generation preclinical studies explore innovative delivery systems, engineered immune cells, and biomaterials to enhance precision and durability, paving the way for future patient-tailored treatments. Created in BioRender. Faas, P. (2025) https://BioRender.com/7w78327. ABSTRACT Autoimmune diseases arise from a breakdown in … Read more
miR-6990 5p, derived from exosomes of MMP14high macrophages, promotes Th17 cell differentiation through the STAT1/RUNX1/ROR-γt signaling axis and enhances IL-17A secretion. This cascade facilitates fibroblast-to-myofibroblast transition and aggravates fibrosis in hypersensitivity pneumonitis. ABSTRACT Th17 cells contribute to pulmonary fibrosis, but the mechanisms driving their differentiation remain unclear. Using single-cell RNA sequencing (scRNA-seq) and a decision … Read more
We analyzed the expression levels of miRNAs in Treg cells and thrombotic parameters in plasma of patients with rheumatoid arthritis (RA) before and after baricitinib (BARI) treatment. Four miRNAs were identified that showed a positive correlation with thrombotic parameters and were associated with an improved therapeutic response to BARI. ABSTRACT Several studies proved that microRNA … Read more
Assessing chromatin accessibility in rare cell populations within tissue remains a key challenge. To address this, we present a low-input ATAC workflow optimized for liver ILCs. The protocol is validated across cell numbers, Tn5 ratios, and library preparation steps and unveils unique epigenetic features of liver NK cells and ILC1s.
The cover image is based on the article Activation of CD8+ T cells in the human ex vivo lung tumor microenvironment using anti-CD3/CD28 and Nivolumab by Tonia Bargmann et al., https://doi.org/10.1002/eji.70060
Tregs exist in two functional states: TNF-producing Tregs, which are expanded in mouse models of chronic inflammation and cancer, and TNFR2-expressing Tregs, which dominate and transmit their phenotype to TNF+ Tregs. The two states are characterized by distinct phenotypic and functional features. Created in BioRender. Piconese, S. (2025) https://BioRender.com/5cldomx. ABSTRACT TNF is a pleiotropic cytokine … Read more
In the absence of Vγ4⁺ and Vγ6⁺ γδ TCRs, Vγ1 T cells only partially compensate for IL-17 production. These Vγ1 T cells develop pre- and postnatally and show enhanced γδ17 gene signature, but are absent in skin, highlighting the nonredundant role of Vγ4⁺ and Vγ6⁺ subsets in IL-17-mediated immunity. ABSTRACT γδ T cells are unconventional … Read more
Fecal extracellular vesicles (fEVs) were isolated from preserved stool samples in DNA/RNA shield and characterized. In an in vitro model with PBMC, fEVs of pregnant women modulate T cells toward a regulatory phenotype favorable for pregnancy compared to fEVs of non-pregnant women. ABSTRACT Pregnancy requires immune tolerance to a semi-allogeneic fetus, involving profound adaptations, particularly … Read more
Patient heterogeneity remains a challenge in the treatment of lung cancer. Here, patient-derived, ex vivo tumor lung slices originating from the tumor-border are used to unravel microenvironment-specific responses to immunotherapies. The focus lies on the impact of the native tumor microenvironment on CD8+ T cell activation after anti-CD3/CD28 or anti-PD-1 treatment. ABSTRACT Despite advancements in … Read more
This mini-review introduces a special issue on γδ T cells in the European Journal of Immunology. It summarizes how recent advances in single-cell multiomics, mouse models, and human studies have clarified the developmental pathways, TCR–ligand interactions, and adaptive-like responses of γδ T cells. A thorough understanding of the complex biology of these cells is necessary … Read more
Immunoglobulin (Ig) A is the main antibody isotype found on mucosal surfaces in mammals, where it is predominantly present as a dimer. Here we provide an easy, scalable, efficient, and broadly applicable method to produce and purify monoclonal mouse dimeric IgA from single B cell Ig transcripts to study mucosal antibody responses at single-cell level.
Nutrient metabolism (glucose, amino acids, lipids) serves as a critical fourth signal in T-cell activation, with its dysregulation promoting autoimmune pathogenesis in systemic lupus erythematosus, rheumatoid arthritis, and multiple sclerosis through metabolic reprogramming, offering potential therapeutic targets. ABSTRACT Abnormal T-cell activation and differentiation are pivotal in the pathogenesis of autoimmune disorders. Traditionally, T cell activation … Read more
The innate actions of the immune system allow for a rapid response to potential threats. Here we show that upon classical T cell activation, both murine and human adaptive immune cells can acquire innate capabilities allowing them to respond to cytokines in a TCR independent manner. ABSTRACT Memory T cells, a sizable compartment of the … Read more
Extracellular vesicles (EVs) contribute to alloimmune responses and inflammation after lung transplantation through their immunogenic cargo (cytokines, miRNAs, MHC, Col-V, and Ka1T). Potential biomarkers (Col-V, Ka1T, LKB1, and HLA-G) may predict acute rejection and CLAD. EV-based therapies during ex vivo lung perfusion and ischemia-reperfusion preclinical models show potential to improve outcomes. ABSTRACT In the field … Read more
Self-regulation of the IL-1 system mediated by the negative regulatory receptors IL-1R8 and IL-1R2 results in tuning of inflammation and metabolic rewiring, as well as lymphoid or myeloid cell immune suppression. IL-1R8 and IL-1R2 are emerging as potential therapeutic targets to modulate immunopathology and re-educate lymphoid or myeloid cells, respectively. ABSTRACT IL-1 family members and … Read more
Using spectral flow cytometry, we analyzed circulating lymphocyte subsets in treatment-naive individuals with multiple sclerosis (MS) and other central nervous system autoimmune diseases (CNS AIDs). Elevated B-cell and CD4+ T-cell frequencies were a disease-specific feature of MS, while reduced T-bet+ and CXCR3+ B-cell levels were associated with progressive disease.
Innate lymphoid cells (ILCs) orchestrate tissue homeostasis and inflammation. Here, we review current understanding of how different subsets of ILCs can contribute to both pro- and anti-tumour immunity depending on the local context. ABSTRACT The innate lymphoid cell (ILC) family includes natural killer (NK) cells, recognised for over 50 years, as well as several more … Read more
Prevotella timonensis, a bacterium present during vaginal dysbiosis, increases cell–cell clustering between primary DCs and CD4 T cells and subsequently enhances CD4 T cell proliferation. These results provide insight into how microbiota directly affect the immunological function of DCs, thereby modulating inflammation. Created in BioRender. Geijtenbeek, T. (2025) https://BioRender.com/t02mfss. ABSTRACT Dysbiosis of the vaginal microbiome … Read more
In this study, we show that caspase-8 inhibition induce maturation in DCs through a synergistic crosstalk between the STING signaling pathway and RIPK1-RIPK3-MLKL pathway, without induction of cell death in the DCs. The mature DCs secrete TNF-α that induces cancer cell death in DC/cancer cell co-cultures upon concomitant caspase-8 inhibition. ABSTRACT Activation of the cGAS-STING … Read more
Rag2−/− mice are unable to clear respiratory syncytial virus (RSV) infection, despite an earlier recruitment of natural killer (NK) cells to the lungs compared with wild-type controls. Furthermore, depletion of NK cells does not affect viral load, indicating that alternative innate anti-viral mechanisms may compensate in the absence of adaptive immunity. ABSTRACT Respiratory syncytial virus … Read more
Our cover features images related to flow cytometry techniques widely used for analysis of function and phenotypes of major human and murine immune cell subsets, superimposed on a multidimensional immune cell population scatter plot. These images are taken from the third edition of EJI’s Flow Cytometry Guidelines by Cossarizza et al., a comprehensive resource prepared … Read more
Dysregulated cytokine secretion and signaling underlie systemic autoinflammatory diseases (SAIDs). Here, we characterized immune dysregulation in SAID patients by profiling cytokine secretion at the single-cell level, establishing measurements for secretion dynamics and cellular polyfunctionality, compared with healthy controls, revealing natural variability within immune responses between donors.
Low-dose SARS-CoV-2 infection in 129 × C57BL/6-K18-hACE2 mice induces sustained lung inflammation. Despite complete viral clearance and full recovery of body weight by day 8 post-infection, both CD4+ and CD8+ T cells remained detectable in the lungs up to day 28 post infection, indicating ongoing immune activity. ABSTRACT Many SARS-CoV-2 patients experience chronic pulmonary symptoms … Read more
SOCS proteins are key modulators of cytokine signaling during SARS-CoV-2 infection, balancing antiviral responses and inflammation. The virus differentially regulates SOCS expression across tissues and disease stages, exploiting SOCS regulatory function to suppress antiviral pathways. This regulatory role positions SOCS proteins as potential targets for stage-specific immunomodulatory therapies. ABSTRACT Suppressor of cytokine signaling (SOCS) proteins … Read more
Mast cell phenotypic features influence anti-bacterial response. Connective tissue-like mast cells sense Salmonella through combined Toll-like-receptor (TLR) signaling and recognition of Type-III-secretion-system mediated invasion. By contrast, due to low TLR expression, mucosal-like mast cells fail to respond to extracellular Salmonella, but their abundant granules limit intracellular colonization by invasive bacteria. ABSTRACT Mast cells (MCs) lodge … Read more
BMPR2 deficiency enhances ILC2 proliferation and exacerbates type 2 airway inflammation. BMP4 restrains ILC2 expansion via canonical BMP signaling, alleviating inflammation in a BMPR2-dependent manner. ABSTRACT 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 … Read more
Mast cells colonise tissues during development and may be involved in maturation processes. In the mammary gland, they are thought to promote pubertal branching morphogenesis. Using new Kit-independent models that are more mast cell-specific, we demonstrate that neither constitutive deficiency nor induced depletion at puberty impairs mammary gland branching. Mast cells are thus not essential … Read more
This review summarises current knowledge of T cell responses induced by flavivirus vaccines being licensed or under development. Existing vaccines against flaviviruses have been developed and analysed primarily in the context of antibody responses, while the role of T cells in contributing to immunity against flaviviruses is less studied. ABSTRACT Flaviviruses are major human pathogens … Read more
Regulatory T cells (Tregs) promote tumor progression and therapy resistance by suppressing antitumor immunity. Here, we identify the antibiotic thiostrepton as a novel Treg-targeting immunomodulator for cancer immunotherapy. Thiostrepton impairs Treg differentiation and suppressive capacity. In an MC38 model, thiostrepton treatment reduced intratumoral Foxp3⁺ Tregs and significantly inhibited tumor growth. ABSTRACT Regulatory T cells (Tregs) … Read more
A single booster injection of allergen extract is capable of rapidly activating B-cellular memory several years after completion of allergen immunotherapy, demonstrated by an increase of allergen-specific IgG-producing cells and IgG/IgG4 antibodies as well as improved allergen-blocking capacity. This indicates that booster injections allow maintenance of long-term allergen tolerance. ABSTRACT Allergen immunotherapy (AIT) of patients … Read more
Mechanism of GCs combined with ICI may induce LAG-3, an inhibitory molecule expression (A) Immune checkpoint inhibitors (ICIs) are a class of drugs that work by blocking inhibitory molecules on immune cells (B) Glucocorticoids (GCs) are used to manage the immune-related adverse events following ICI therapies (C) Concomitant GCs with ICI therapies can induce peripheral … Read more
