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
Local and systemic neuroimmune interactions involving innate lymphoid cells (ILCs) shape organismal physiology and defence. Neuro-ILC circuits operate across different organs through brain–body and inter-organ communication axes. These neuroimmune circuits integrate external environmental cues and internal physiological signals to regulate organ physiology, thermogenesis, metabolism, endocrine function, and organismal health. ABSTRACT Over the past decade, innate … Read more
• Dysregulated HLA-DR expression on γδ T cells and impaired functionality of αβ T cells were found in the bone marrows of AML patients. • The ex vivo-expanded donor γδ T cells with high expression of HLA-DR facilitated the cytotoxic effect of αβ T cells. ABSTRACT In addition to exhibiting significant cytotoxic capabilities, γδ T … Read more
Exploiting a high-dimensional mass cytometry approach, we demonstrate that CD56+ lymphocytes promote Mycobacterium tuberculosis dormancy by delivering granulysin, a cytotoxic effector molecule with known antimicrobial activity. ABSTRACT Human tuberculosis (TB) caused by Mycobacterium tuberculosis (Mtb) remains a global public health threat. Granulomas constitute a hallmark of TB pathogenesis that can clear, contain, or exacerbate an … Read more
SOCS mimetics target dysregulated cytokine signaling, offering promising immunomodulatory therapy for autoimmune encephalitis by suppressing cytokine signaling, reducing neuroinflammation, and preserving blood–brain barrier integrity. ABSTRACT Autoimmune encephalitis (AE) is a debilitating neurological condition characterized by the immune system’s attack on neuronal cells, often leading to significant cognitive and neurological impairments. Autoantibodies, particularly those targeting N-methyl-D-aspartate … Read more
T cell receptor engagement induces coordinated actin and microtubule cytoskeletal remodeling at the immunological synapse. This dynamic reorganization generates mechanical forces that sustain TCR signaling and promote effective T cell activation. The SSH1–cofilin–LIMK1 signaling pathway plays a pivotal role in regulating cytoskeletal dynamics during this process. ABSTRACT During T cell immune responses, actin dynamics facilitates … Read more
This study discovered the small molecule 9-methoxy-6-methylindolo[3,2-b] quinoxaline (IFA005) as a potent immunomodulator capable of converting human memory CD4⁺ T cells into functional Foxp3⁺ regulatory T cells. IFA005 suppresses Th2 cytokines (IL-4, IL-5, and IL-13) and promotes the iTreg phenotype by inhibiting Wnt/β-catenin signaling through NKD2 upregulation. These findings support small-molecule-mediated Wnt/β-catenin blockade as a … Read more
Autoantibodies in ulcerative colitis target neutrophil and mucosal components, including NETs, goblet cells, and integrins-offering insight into disease pathophysiology. Understanding these interactions may support biomarker development, enable earlier diagnosis, aid patient stratification, and drive future therapeutic innovation. ABSTRACT Ulcerative colitis (UC) is a chronic inflammatory bowel disease characterized by immune dysregulation and epithelial barrier dysfunction. … Read more
We investigated neutrophil heterogeneity in patients with systemic lupus erythematosus and identified increased surface levels of LAMP1 (CD107a). Stimulation of healthy donor neutrophils led to increased surface LAMP1. Urine and serum soluble LAMP1 levels were increased in patients, especially those with proliferative lupus nephritis. ABSTRACT Lupus nephritis (LN) is a severe manifestation of systemic lupus … Read more
Testosterone suppresses Th17 cell differentiation and alleviates Th17-driven skin inflammation in an experimental psoriasis model. Mechanistically, testosterone binds to the ligand-binding domain (LBD) of RORγt, inhibiting its transcriptional activity required for IL-17 production and other Th17-cell-associated proinflammatory gene expression. These findings provide a mechanistic explanation for testosterone’s immunosuppressive effects and offer insights into the gender … Read more
Blood CD8 T cells in mice with advanced liver fibrosis exhibit IFN-γ and granzyme B hyperfunction, and animal responses to ectopic tumour challenge and immunotherapy are impaired. ABSTRACT Immune dysfunction in liver disease contributes to significant morbidities, depending on liver damage severity and aetiology. We previously reported long-lasting generalized CD8 T cell hyperfunction in chronic … Read more
• SLAM family receptors regulate the susceptibility of hematopoietic stressed cells to NK cell-mediated cytotoxicity. • Leukemia cells might downregulate the expression of SLAM family receptors to avoid being recognized and lysed by NK cells. • NK cell engagers containing SLAM family receptors may be an important resource for the design of therapeutic strategies aiming … Read more
In N-ERD patients, oral aspirin-induced bronchospasm is associated with increased blood group 1 innate lymphoid cells (ILC1s), decreased sputum eicosanoids, and increased urinary leukotriene E4 (LTE4), suggesting a potential role of blood ILC1s in aspirin-induced bronchoconstriction. ABSTRACT Previous studies confirmed increased group 2 innate lymphoid cell (ILC2s) count in nasal scrapings, alongside a reduced blood … Read more
During filarial nematode infection with Litomosoides sigmodontis, PD-L2 down-regulates Th2 cell expression of GATA-3 and Th2 cytokines and enables parasite survival. Concurrently, B cells suppress protective immunity through a mechanism that does not involve PD-L2. ABSTRACT Filarial nematodes infect over 200 million people, predominantly stimulating a Type 2 immune response. Protective immunity takes decades to … 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
Using scRNAseq and spatial analysis, we analyse cDC1 states and spatial distribution in tumours during immune-mediated rejection. We identify two cDC1 activation states, each occupying different regions and associated with distinct CD8+ T cell populations. This reveals the spatial organisation of cDC1 states that may be key to anti-tumour immunity. ABSTRACT CD8+ T cells are … Read more
Conditionally replicating oncolytic adenoviruses (OAds) mediate cancer cell destruction while triggering robust immune responses. Clinical data reveal their ability to remodel the tumor microenvironment and enhance responsiveness when combined with other therapies. This review highlights immune-modulating effects of OAds in patients, with a focus on therapeutic implications and combination strategies. ABSTRACT Oncolytic immunotherapy, particularly using … Read more
In a patient with the classical clinical phenotype of STAT3-hyper-IgE syndrome, we identified the previously unreported STAT3 variant p.K709N to be disease-causing. Molecular analyses revealed that STAT3 p.K709N exerts a dominant-negative effect, leading to impaired STAT3 dimerization and reduced STAT3 target gene expression. Source: Created in BioRender. Hagl B. (2025) https://BioRender.com/80tycxp. ABSTRACT STAT3-hyper-IgE syndrome (STAT3-HIES) … Read more
The immunodominant pan-coronavirus epitope iCope spans amino acids 816–830 within the fusion domain of the SARS-CoV-2 spike glycoprotein. This region exhibits a comparatively low mutation rate, especially when contrasted with the receptor-binding domain (RBD). Antigen-specific T cell responses against iCope are detectable even in unexposed individuals, are modestly enhanced following SARS-CoV-2 infection, and are robustly … Read more
Schematic diagram of DCpep-NM-PLGA-rOmpW preparation and its immunoprotective effects on acute lethal pneumonia. This study developed a biomimetic nanovaccine (DCpep-NM-PLGA-rOmpW) against A. baumannii. The nanoparticle-delivered multiepitope vaccine induced robust Th1/Th17 and antibody responses, demonstrating significant protection in a lethal pneumonia model. ABSTRACT The development of vaccines represents a promising and safe strategy to combat multidrug-resistant … Read more
Machine learning analysis of serum immune factors clustered SARS-CoV-2 patients into moderate (balanced-immune-modulation [BIM]) and severe groups; the latter composed of two distinct and opposite immune patterns (down-immune-modulation [DIM] and up-immune-modulation [UIM]). DIM/UIM and BIM clusters show different clinical, laboratory and immune parameters including T and B lymphocytes. ABSTRACT The complex pathophysiology of severe acute … Read more
Studying local immune responses in IBD remains challenging. This study demonstrates that precision-cut intestinal slices from IBD patients mimic key immunopathological features ex vivo and respond specifically to immune stimuli. This model allows direct pharmacological modulation of patient tissue ex vivo and offers a powerful platform for translational research. ABSTRACT Inflammatory bowel disease (IBD) affects … Read more
NK cells quickly upregulate LAG3 upon activation. LAG3+ NK cells present hallmarks of immune exhaustion. The role of LAG3 in imposing NK cell dysfunction remains to be elucidated. ABSTRACT NK cells are critical for immunosurveillance, yet become dysfunctional when chronically stimulated by virally infected or cancerous cells. This phenomenon is similar to T cell exhaustion … Read more
This review examines platelet-based nanotechnology in cancer immunotherapy, leveraging platelets’ innate properties via membrane-mimicking systems and engineered platelets to enhance targeting, immune responses, and efficacy, while outlining future directions for its applications in cancer treatment. ABSTRACT Cancer immunotherapy is a cornerstone of precision medicine, yet its efficacy is often hampered by the immunosuppressive and heterogeneous … Read more
Positively selected autoreactive B cells (C1-Bsup) specific for collagen type II (COL2) suppress inflammation, while pathogenic COL2-specific plasma cells (CB20 clone) drive it. The balance between suppressive and pathogenic autoreactive responses governs tissue homeostasis. ABSTRACT The adaptive immune system is shaped by self-recognition, creating a paradox where autoreactivity is essential for immune regulation, yet implicated … Read more
Regulatory T cells rely on mitochondrial respiration to exert their anti-inflammatory functions and maintain immune homeostasis. Our study demonstrates that while teriflunomide inhibits effector T cells, it may also impair Treg metabolism and promote a dysfunctional, proinflammatory phenotype. Created in BioRender. Dyczko, A. (2025) https://BioRender.com/vl0s1vk ABSTRACT Regulatory FOXP3+ T cells (Tregs) have been characterized with … Read more
Our study delineates the molecular mechanisms employed by HOXB4 in regulating both Th2 and Th9 cell differentiation. We show that HOXB4 differentially regulates the secretion of different signature cytokines like IL-9 in a cell-specific manner, either directly or indirectly influencing their promoters by binding partner proteins like PU.1. ABSTRACT CD4+ T helper cells are involved … Read more
Chronic mucocutaneous candidiasis can be caused by an Inborn Error of Immunity, especially those affecting TH-17 / IL-17 responses. Through in-depth immunophenotyping and functional assays, we reveal the association between homozygous carriage of the common p.R381Q IL-23R genetic variant and increased candidiasis susceptibility, relying on disrupted IL-23-mediated IL-17 immunity.
Biomarkers of vascular integrity and inflammatory processes are involved in different types of angioedema, highlighting the potential importance of complement/lectin system interactions with granulocytes in understanding angioedema triggers. The C1s/C1-INHc-to-MASP-1/C1-INHc ratio could be used as a diagnostic tool to distinguish C1-INH-HAE from other HAE subtypes. ABSTRACT The precise molecular mechanisms underlying angioedema attacks in cases … Read more
Mycobacterium tuberculosis infection of human monocyte-derived macrophages during febrile conditions significantly induces heat shock protein-70 (HSP70) expression, which modulates cytokine responses. This highlights that pathophysiological responses, such as fever, regulate tuberculosis immunopathology. ABSTRACT Fever is a common clinical symptom in patients with tuberculosis (TB). During fever, heat-shock proteins (HSPs), such as HSP70, are expressed, which … Read more
The Sialic acid/Siglec axis is emerging as an important target in the TME. We explore the role of sialylation within stromal-rich, immunosuppressive TMEs, focusing on how specific sialic acid/Siglec interactions dictate innate and adaptive immune responses. We propose that targeting glycoimmune checkpoints as a mechanism may overcome stromal-mediated therapy resistance and enhance anti-tumour immunity. ABSTRACT The … Read more
The T cell response induced by SARS-CoV-2 vaccines is an essential component of immune protection against COVID-19. Multiparametric flow cytometry analysis emerges as a valuable tool for in-depth assessment of T cell phenotype nuances that occur after booster vaccination, such as a fifth dose of an inactivated SARS-CoV-2 vaccine. Figure created with BioRender.com.
Innate lymphoid cells contribute to the health of the uterine microenvironment, which is important for global health. Endometriosis affects 10% of women of fertile age. Millions of pregnancies have adverse outcomes every year: miscarriages, pre-eclampsia, fetal growth restriction, preterm labour and stillbirth — all due to defective placentation. Abnormal fetal growth exposes newborns to greater … Read more
Ak2 deficiency leads to impaired development of T and B cells in mice, corresponding to impaired lymphopoiesis of reticular dysgenesis (AK2 deficiency) in humans. In contrast to the human pathophysiology, Ak2 deficiency is lethal in mice due to severe anaemia, and murine myelopoiesis is less affected. ABSTRACT Reticular dysgenesis (RD) is a rare genetic disorder … Read more
Human interferon-ω (IFN-ω) is produced by monocytes and plasmacytoid dendritic cells in response to inflammatory stimuli. It confers antiviral protection to lung epithelial cells against SARS-CoV-2 infection and enhances the effector functions of antigen-specific CD8⁺ T cells. ABSTRACT The type-I interferon family is well known for its critical role in innate immunity. It comprises several … 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
nuTCRacker aims to predict unseen αβTCR-peptide-HLA-I affinity. Predictions are successful for only a subset of unseen peptides although they are better than the benchmarked methods. Predictions are tested on both novel and published T cell assays. ABSTRACT The ability to predict which antigenic peptide(s) the αβTCR of a given CD8+ T-cell clone can recognise would … Read more
In this study of 458 patients post-COVID-19, nearly half developed postacute sequelae (PASC). While humoral and inflammatory markers were tied to COVID-19 severity, not PASC itself, individuals with PASC showed distinct T cell alterations, especially terminally differentiated, SARS-CoV-2-specific CD4+ T cells. A machine learning model identified T cell phenotypes as key PASC predictors. ABSTRACT Post-acute … Read more
The authors demonstrate that current aP vaccines induce IL-10-secreting CD4+ and CD8+ Treg cells that suppress IL-17-secreting respiratory tissue-resident memory (TRM) cells, and thereby fail to prevent nasal infection with B. pertussis. Blocking IL-10R in vivo or adding a novel adjuvant LP-GMP and intranasal delivery reverses suppression and enhances vaccine efficacy. Created with BioRender.com. ABSTRACT … Read more
This review examines inborn errors of immunity (IEIs) affecting γδ T cells, focusing on conditions that lead to their altered balance with αβ T cells. It highlights key molecular players and species differences in human and mouse models, offering insights into γδ T cell development and function with potential diagnostic and therapeutic implications. ABSTRACT Gamma … Read more
Utilising a remote force application platform, MICA, we identify that force application to the TCR-CD3 complex using anti-CD3ε functionalised magnetic nanoparticles is capable of inducing TCR signalling and CD4+ T-cell activation. Force application promotes cell surface TCR clustering, triggering T-cell activation through NFAT-pathway signal accumulation. ABSTRACT Mechano-modulation of cell surface proteins to influence cell activation … Read more
CD8+ T cells isolated from male donors exhibit greater IL-15–driven bystander activation, NKG2D expression, and cytotoxicity than female CD8+ cells. This study reveals a sex-based difference in innate-like T cell function that may contribute to worse viral disease outcomes in males. ABSTRACT The recent COVID-19 pandemic has highlighted a significant sex bias in disease outcome, … Read more
Frequencies of circulating T peripheral helper (cTph) and activated T follicular helper (cTfh) cells increase close to the diagnosis of clinical type 1 diabetes, but not at the onset of autoimmunity. Single-cell analysis reveals cTph as a heterogeneous cell population, sharing features both with cTfh and other memory T cells. ABSTRACT Circulating follicular (cTfh) and … Read more
Cytotoxicity-associated genes exhibit heterogeneity at the cellular and tissue levels (left). NKG7 gene expression is strongly associated with a cytotoxic gene signature (middle). NKG7 expression is stable and consistently detected in cells across immunologically relevant tissues and within tumor-infiltrating immune cells (right). Figure generated in collaboration with Susan Stone (https://www.sue-stone.com). ABSTRACT Cytotoxicity is a cornerstone … Read more
This review explores how single-cell sequencing and multiomics reveal cell states and communication networks involved in autoimmunity. We highlight insights into antigen specificity and autoreactive lymphocytes, uncovering mechanisms like molecular mimicry. We discuss genetic susceptibility loci in healthy and disease tissues and the challenges and opportunities in integrating different approaches to better understand autoimmune disease. … Read more
