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
• CD4+ and CD8+ tissue-resident memory T (TRMs) cells which are CD103+PD-1+CD25+ICOS+ and, CD4+CD103−PD-1+CXCR5+CCR5+/− T follicular helper/T peripheral helper (Tfh/Tph) cells infiltrate lesional relative to nonlesional skin in atopic dermatitis (AD). • Frequencies of CD4+CD103+PD-1+TRMs, monocyte-derived dendritic cells (Mo-DCs), and inflammatory monocytes positively correlate with disease severity (EASI) within AD lesions. ABSTRACT Atopic dermatitis (AD) … Read more
IL-4, IL-15, and type I IFN coordinately shape the heterogeneity of CD44hi CD49d– VM CD8 T cells. IL-4 acts specifically on Ly6C+ Sca-1− cells, while IL-15 promotes the development of both Ly6C+ Sca-1− and Ly6C− Sca-1− VM subsets. Type I IFN signaling primarily regulates Sca-1+ populations. Functionally, Ly6C+ and/or Sca-1+ subsets exhibit enhanced IFN-γ and … Read more
This review explores the structure and function of meningeal immunity throughout development. It highlights key differences in immune cell composition, lymphatic development, and neuroimmune interactions between neonates and adults, offering insights into neonatal vulnerability to CNS infections and potential avenues for future research. ABSTRACT The central nervous system (CNS) is responsible for controlling the entire … Read more
CD8+ T cells exhibit dual roles at the maternal-fetal interface supporting tolerance via IL-10 and TGF-β and aiding implantation and vascular remodeling through TNF-α and IFN-γ. In HIV infection, CD8+ T cells expand, driving inflammation, PD-L1 upregulation on trophoblasts, and cytotoxic dysfunction via reduced Granzyme B and Perforin, compromising placental immunity. ABSTRACT The global HIV … Read more
Dipeptidyl peptidase 9 (DPP9) inhibition with novel compounds induces lytic cell death in human leukocytes. We report that this cell death occurs via DPP9, inflammasome-activated caspase-1, GSDMD, and GSDME. Additionally, DPP8/9 activity is upregulated in monocyte-to-dendritic cell differentiation and DPP9 localizes both to the cytoplasm and the nucleus in leukocytes. ABSTRACT Dipeptidyl peptidase 9 (DPP9) … Read more
Ascites is one hallmark of decompensated liver cirrhosis. NK cells in cirrhosis-associated ascites are a heterogeneous group of cells with altered functionality and CD103 expression identifies a subpopulation that is likely to be induced by cytokines present in the ascites fluid. ABSTRACT The occurrence of ascites is a frequent complication associated with the decompensation of … Read more
Resolution of EAU at 90 days after induction is dependent on CCL20. During the resolution of EAU, the emergence of regulatory T cells (post-EAU Tregs) in the spleen that suppress EAU is dependent on CCL20. However, post-EAU Tregs do not require CCL20 to suppress EAU. ABSTRACT Uveitis is a leading cause of blindness worldwide and … Read more
Single-cell RNA sequencing of enzymatically dissociated human lymph node stromal cells (LNSCs) reveals transcriptional and spatial heterogeneity. Following cell sorting and phenotyping, stromal subsets were validated across multiple datasets, mapped within lymph node architecture, and analyzed for subset-specific immune interactions, enabling a comprehensive reconstruction of the LNSC landscape and its role in lymph node organization … Read more
Bone marrow CD8+ T cells from patients with MDS and CMML show decreased TCR diversity compared to AML. Treatment with the hypomethylating agent azacitidine in MDS and CMML alters TCR repertoire of CD8+ T cells without affecting TCR diversity.
mTOR is binding to NLRP3 until a NLRP3-inflammasome stimulus. After activation, mTOR is translocated to the nucleus to inhibit STAT1 and support the NLRP3 inflammasome assembly and activation. mTOR inhibition with rapamycin reduces mTOR presence in the nucleus and increases STAT1 which represses NLRP3 inhibiting the activation. ABSTRACT The NLRP3 inflammasome has emerged as an … Read more
Butyrate, a short-chain fatty acid (SCFA) derived from dietary fibers, selectively inhibits human mast cell activation by targeting transcription start sites (TSS) and super-enhancers regulating key mast cell genes. Local histone hypoacetylation induced by butyrate likely drives transcriptional suppression and reduced degranulation, providing new insights into how SCFA modulates inflammation. ABSTRACT Mast cells are key … 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
A critical configuration of nanoscale a-APCs displaying high valency of tumor-specific peptide-MHCs and co-stimulatory molecules is essential for expanding antigen-specific CD8+ T-cells ex vivo at high yield with profound production of cytolytic molecules, resulting in enhanced therapeutic potential for inhibiting the growth of solid tumors. ABSTRACT Adoptive T-cell therapy is an emerging immunotherapeutic strategy for … Read more
Recent works indicate that several X-linked genetic mechanisms contribute to the female predisposition for autoimmune diseases. Here, we review the recent findings that underscore the significance of the alteration of X chromosome inactivation (XCI) maintenance and the putative role of the long noncoding XIST/Xist RNA in this process but also as a sex-biased source of … Read more
Regulatory cell-based therapies, encompassing stem-like cells, T regulatory cells, and tolerogenic dendritic cells, have already been tested in clinical trials for reversing autoimmunity in type 1 diabetes. These early successes opened new perspectives for next-generation antigen-specific strategies to achieve durable and self-sustaining immune tolerance. ABSTRACT Type 1 diabetes (T1D) is an autoimmune disorder characterized by … Read more
Summary of findings showing proposed effects of RSV-induced Kdm5b in the DC resulting in the exasperated lung pathology seen with RSV related to modified type 1 responses. ABSTRACT We previously observed an upregulation of Kdm5b, an H3K4 demethylase, following RSV infection of DCs that regulates key innate cytokines, including Type I IFN and TNF. As … Read more
Expansion of the adaptive NKG2C+ NK cells during cytomegalovirus (CMV) infection is restricted to the subset lacking NKR-P1A receptor. This is associated with increased proliferation of NKR-P1A‒, but not NKR-P1A+, NK cells in CMV-infected individuals. ABSTRACT The impact of cytomegalovirus (CMV) infection in shaping natural killer (NK) cell receptor (NKR) repertoire highlights the importance of … Read more
The development of new technologies for generating monoclonal antibodies has made it possible to extend the use of monoclonal antibodies for controlling viral infections. Here, we discuss the advances in antibody cloning techniques and the current use of passive immunization both as a preventative measure and treatment of viral infection. ABSTRACT The basic concepts of … Read more
Mutations in the non-coding RNA gene RNU4ATAC are associated with growth restriction and complications related to antibody deficiency. Here, we report that innate immune dysfunction is a previously unrecognised feature of this disorder. In particular, painful chilblain-like lesions are common in RNU4ATAC patients and are linked to dysregulated type I interferon signalling.
This review highlights how genetic mutations impairing antiviral signaling pathways increase susceptibility to viral infections. The findings emphasize the importance of genetic screening and personalized treatment strategies to manage infectious risks and tailor vaccine protocols for genetically susceptible individuals. ABSTRACT The innate immune system relies on nucleic acid (NA) sensors to detect viral infections and … Read more
To link IFNγ-secretion levels of epitope-specific T-cells with their TCRαβ, we coated nanovials with pHLA-I to capture and activate epitope-specific T-cells and their secreted IFNγ, followed by index-sorting and TCRαβ sequencing. We demonstrate that nanovials are a promising tool to link single epitope-specific TCRαβ clonotypes to the cell’s functional properties.
Through the analysis of TCR repertoires, differential gene expression, and flow cytometry, we propose a mechanism in which surface CD69-negative memory T cells reside in the bone marrow of healthy humans. Therefore, we challenge the notion of surface CD69-positive T cells representing the only bona fide resident phenotype in the bone marrow. ABSTRACT Across tissues, … Read more
Human CD8+ and CD4+ memory and regulatory T-cell subsets, but not naïve or effector cells, may become CD69+ bone marrow-resident cells, suggesting that they could be maintained long-term as quiescent cells. CD4+ memory T-cells and EOMES+Tr1-like cells, respectively, expressed IL-7Rα and IL-15Rβ, suggesting that they compete for different homeostatic niches. ABSTRACT Maintenance of memory T-cells … Read more
T follicular helper (TFH) cells provide essential help to B cells in germinal centers (GCs). TFH and GC B cell responses are long-lasting in draining mediastinal lymph nodes of Litomosoides sigmodontis-infected BALB/c mice, a rodent model of filarial infection. ABSTRACT T follicular helper (TFH) cells are the primary CD4+ T helper cell subset providing help … Read more
This review article summarizes the currently available information on the functions of atypical IκB proteins including Bcl-3, IκBNS, and IκBζ, which have been studied mostly in mouse models. We focus on the regulation of these modulators of transcription, describe their role in lymphocyte differentiation, and their involvement in the development of autoimmunity. ABSTRACT Signaling pathways … 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
Although VSIG4+ LPMs and VSIG4− LPMs are identical at the transcriptomic and surface proteomic level, VSIG4+ LPMs are superior phagocytes that protect against CRC peritoneal outgrowth and influence the early phase of T. brucei brucei infection. ABSTRACT Large peritoneal macrophages (LPMs) play a role as gatekeepers of peritoneal homeostasis by providing a first line of … Read more
During Plasmodium infection, inflammatory monocytes upregulate ACOD1, leading to increased production of the anti-inflammatory metabolite itaconate. While ACOD1 deletion has no effect in the lethal PbNK65-E model, it exacerbates disease in the milder PcAS model. These findings highlight a modest but context-dependent protective role for itaconate in malaria. ABSTRACT In severe malaria, dysregulated metabolism and … Read more
Toll-like receptor 10 (TLR10 or CD290) shares the same structural organization as the other TLRs but shows a unique expression pattern and distinct functional activities yet to be fully elucidated. This review summarizes key steps and recent updates on TLR10 research including open questions and future perspectives. ABSTRACT Toll-like receptors (TLRs) are transmembrane proteins that … Read more
The acute depletion of Tregs induces activation of APCs and Tconvs, eventually leading to autoimmune disease. This activation could only be prevented by the blockade of CD80/CD86, so CD80/CD86-CTLA-4 interactions appear to be the most important Treg suppressor mechanism in the maintenance of immune homeostasis in the steady state. ABSTRACT Foxp3+ regulatory T cells (Treg) … Read more
Upon repeated target cell contact serial degranulating NK cells are identified by multiple staining events using differentially labeled anti-CD107a (LAMP1) antibodies. This flow-cytometry-based method allows for the characterization and isolation of serial degranulating NK cells.
Severe COVID-19 disease is accompanied by high plasma levels of proinflammatory, prothrombotic NETs, and NET-inducing cytokine IL-18. We found that both, IL-18 and NETs, are elevated in men with severe disease, but not in women of the same category. Our findings warrant further investigation of sex-related differences in SARS-CoV-2 infection.
Multiple immunizations of mice with Plasmodium berghei radiation-attenuated sporozoites (Pb RAS) induce durable protective immunity, provided that 1° sporozoite (spz) challenge occurs early or within 10 months following the most recent RAS boost immunization. Delaying 1° challenge results in parasitemia. Pb RAS develops partially into early liver stages, is unable to progress to blood-stage parasites, … Read more
IgE induces stronger ER stress than IgG1 due to its constant region, particularly the Cε3 domain, which binds BiP more efficiently. Genetic and structural analyses confirmed IgE’s higher BiP-binding capacity. ER stress, driven by IRE1-XBP1 signaling, regulates plasma cell differentiation, suggesting IgE-specific mechanisms in immune responses.
Analysis of the T-cell epitope landscape of SARS-CoV-2 suggests T-cell intrinsic factors as likely modulators of disease severity and that the capacity of MHC-peptide presentation remains stable among circulating SARS-CoV-2 viral strains. ABSTRACT Infection with SARS-CoV-2 results in mild to severe COVID-19 disease courses. Several studies showed the association of impaired T-cell responses and certain … Read more
Probiotics administered to pregnant mice led to increased frequencies of IL17-committed Vγ6⁺ γδ T cells in the neonatal lung. This highlights a microbiota-sensitive pathway where maternal probiotics enhance γδ17 commitment in the perinatal lung. ABSTRACT The early life period is increasingly being recognized as a window of opportunity to shape immunity, where microbiota and related … Read more
A gluten-free diet prevents Type I diabetes in NOD mice. We characterized T cells from prediabetic mice on gluten-free or standard diets using flow cytometry and single-cell transcriptomics. A gluten-free diet enhanced T-cell activation and effector differentiation, including regulatory T cells, suggesting immune modulation as a mechanism for diabetes prevention. ABSTRACT Nonobese diabetic (NOD) mice … Read more
In children with chronic non-bacterial osteomyelitis, clinical and transcriptional changes in peripheral blood were examined after pamidronate treatment. Clinically effective treatment with pamidronate was associated with reduced expression of two genes (TRDV2 and TRGV9) that encode the subunits of the Vγ9Vδ2 T-cell receptor.
The evolution of the concept of the immune system from a set of composed cells and tissue that defend the host from exogenous agents into a system that has regulatory and homeostatic functions determined by the interaction with microorganisms as a functional part of an extended immune system, that we call symmunobiome. ABSTRACT The immune … Read more
The RNA-binding proteins ZFP36L1 and ZFP36L2 regulate in T cells the production of the key effector molecules TNF, IL-2, and IFNγ. Genetic deletion of ZFP36L1 and ZFP36L2 induces superior cytokine production in continuously activated tumor-infiltrating lymphocytes. However, ZFP36L1+ZFP36L2-deficient T cells exhibit reduced cell fitness: they more frequently undergo apoptosis, potentially due to disrupted cell cycle … Read more
Dimethyl fumarate (DMF) inhibits T-cell proliferation and induces apoptosis by depleting glutathione (GSH) and accumulating reactive oxygen species (ROS). Here, we show that DMF-induced oxidative stress disrupts multiple cell-signaling pathways, including MYC, leading to cell cycle arrest and impaired proliferative responses in activated T-cells. ABSTRACT Recent evidence indicates that the TCA cycle metabolite fumarate plays … Read more
The supernatant of M. tuberculosis-stimulated B cells promotes monocyte polarization toward an anti-inflammatory CD16⁺CD163⁺CD206⁺PD-L1⁺ phenotype via an IL-6/STAT3 pathway. Confirmed with B cells from TB patients, this pathway impairs monocyte proinflammatory functions and may contribute to immune suppression in tuberculosis. Created in BioRender. Neyrolles, O. (2025) https://BioRender.com/930ras3 ABSTRACT The polarization of the monocyte/macrophage compartment toward an … Read more
T-cell recognition of microbiota-derived epitopes is key to immune homeostasis. Here, we used an unbiased screening platform to identify novel immunogenic epitopes from Akkermansia muciniphila and Bacteroides thetaiotaomicron. We demonstrated that these epitopes are conserved across multiple other bacterial strains, suggesting their potential relevance in broader immune interactions. ABSTRACT Antigen-specific recognition of microbiota by T … Read more
Metabolic antagonism in the TME suppresses CD8+ T cell function by depleting essential nutrients and generating toxic byproducts. Metabolic symbiosis between tumor cells and TAMs fosters an immunosuppressive microenvironment. Disrupting metabolic interactions can overcome immune suppression, boost antitumor immunity, and enhance immunotherapy efficacy. ABSTRACT The fate of immune cells is fundamentally linked to their metabolic … Read more
Autoantibodies neutralizing Type I interferons increase the risk of severe viral diseases and are linked to autoimmune conditions. The automated VIDAS assay is suitable for anti-IFN-α2 IgGs quantification, offering a swift, reliable, user-friendly, single test for clinical management.
Here we show that CST and SHLD are required for CSR, while SHLD1-CTC1 interaction via the SHLD1 LDLP motif is dispensable. Mechanistically, we show that CTC1 and SHLD1 are epistatic during CSR, preventing genetic instability, exacerbated DSB end-resection, and microhomology-mediated end-joining at Igh switching sites. Created in Biorender.com. ABSTRACT Downstream of 53BP1-RIF1 lies the Shieldin … Read more
The gut commensal Clostridium sporogenes metabolizes dietary tryptophan into indole-3-propionic acid (IPA). In this review, we highlight recent findings suggesting that IPA acts as an effective signaling molecule, modulating the function of Th17 lymphocytes and resulting in protection against intestinal inflammation. ABSTRACT In recent years, we have witnessed a rapidly growing interest in the intricate … Read more
Neutrophil extracellular traps (NETs) in type 2 diabetes induce a pro-fibrotic but functionally impaired phenotype in cutaneous fibroblasts, associated with collagen breakdown by NET-bound MMP-9. IL-8 released in NETs promotes its own expression in both neutrophils/fibroblasts and neutrophil MMP-9 production, creating positive feedback loops that hinder wound healing. ABSTRACT Neutrophils interact with and activate fibroblasts … Read more
Extracellular calcium induces MET release from human macrophages. Concurrently, extracellular calcium activates the NLRP3 inflammasome. Citrullinated histones, MMP12, MPO and ASC specks are bound to METs and are released by rupture of the plasma membrane, where they exhibit bactericidal properties. ABSTRACT Macrophages can respond to infection or cellular stress by forming inflammasomes or by releasing … Read more
Immune cells and stromal cells undergo metabolic reprogramming in both rheumatoid and osteoarthritis. This review summarises current evidence on the metabolic changes within and the crosstalk between immune and stromal cells in these diseases. In addition, we explore the therapeutic potential of targeting metabolic processes for the treatment of arthritis. ABSTRACT Metabolic reprogramming of stromal … Read more
IgA autoantibodies have been implicated in promoting inflammation associated with rheumatoid arthritis by engaging Fc receptors on myeloid cells. However, underlying mechanisms are still poorly defined. Here, we identified immune complexed IgA2, but not IgA1, to induce hyper-inflammatory macrophages, and that it is dependent on ATP synthase and COX2 activity. ABSTRACT IgA can form immune … Read more
TTP controls the mRNA stability of multiple inflammatory cytokines. Despite a multiorgan inflammatory phenotype, TTP-deficient mice are protected from experimental colitis, in part, through the expansion of IL-22-producing ILC3 in the gut. ABSTRACT Tristetraprolin (TTP, encoded by Zfp36) is an RNA-binding protein that plays a major role in the control of inflammation. Zfp36−/− mice spontaneously … Read more
Bacterial antigens primarily induce BDNF release from platelets interacting with monocytes in PBMCs. This interplay underscores how immune-blood cell complexes shape BDNF levels which may impact early human development. ABSTRACT The gut microbiota and the immune system are closely connected, influencing early-life brain development. Brain-derived neurotrophic factor (BDNF), crucial for neuronal development, has been demonstrated … Read more
RNPC3, as a unique minor spliceosome component, plays a critical role in T cell-dependent immune response. By facilitating minor intron splicing, RNPC3 promotes the proliferation of activated B cells and prevents their apoptosis, thereby supporting the formation of early germinal center B cells. ABSTRACT Germinal center (GC) response ensures the generation of diverse and high-affinity … Read more
In CD8+ T cells, PDCD5 is an activation-induced molecule that interacts with PRDM9, thereby promoting its nuclear translocation and facilitating the H3K4me3 modification of genes associated with effector differentiation. ABSTRACT Epigenetic modification plays a crucial role in establishing the transcriptional program that governs the differentiation of CD8+ effector T cells. However, the mechanisms by which … Read more
Tumor-produced ICAM-1 protein binds to IgG1 antibodies and suppresses their antibody-dependent cellular (ADCC) and complement-dependent (CDC) cytotoxicity against antigen-positive cells via reduced engagement with CD16a receptors on immune effector cells and C1q complement protein. This interaction also reduces antibody internalization that negatively affects antibody–drug conjugate cytotoxicity. ABSTRACT Humoral immunity utilizes antibodies and immune effector cells to … Read more
JAK inhibitors (baricitinib, tofacitinib, upadacitinib), except for filgotinib, significantly reduce plasmablast differentiation but only partly inhibit activation of naïve B cells and exert a more modest effect on TNF and IL-8 production. Unlike other JAK inhibitors, filgotinib selectively inhibits STAT5 phosphorylation without affecting STAT3 phosphorylation in response to IL-21. ABSTRACT B cells play a crucial … Read more
The 1E03 immunoglobulin knock-in mouse produces B cells reactive to deamidated gluten peptides (DGP). The transfer of DGP-specific B cells and immunization with a DGP-cholera toxin conjugate led to the formation of DGP-reactive small-intestinal lamina propria plasma cells and serum antibodies. This model enables studies of plasma cells associated with celiac disease. ABSTRACT Celiac disease … Read more
A mutation was identified in 47% of the CVID-enrolled patients and, in the majority, it was not related to CVID according to the IUIS classification, leading to a diagnostic metamorphosis of this pathological entity. The Mo-CVID Score could help clinicians prioritize genetic analysis in pediatric CVID patients. The image was created with BioRender.com. ABSTRACT Common … Read more
In crucian carp (Carassius auratus), TLR3 and TLR5 can cross-sense the dsRNA analogue poly (I: C) and bacterial flagella, activating the associated immune response. It is an evolutionary strategy for fish to tackle various pathogens in aquatic environment. ABSTRACT Toll-like receptors (TLRs) play a crucial role in the immune response to pathogen invasion. The TLR … Read more