European Journal of Immunology

LPS-stimulated macrophages exhibit high glycolytic flux, with pyruvate preferentially converted to lactate even under normoglycemic conditions, limiting pyruvate availability for the tricarboxylic acid (TCA) cycle and reducing oxygen consumption rate (OCR). Glucose deprivation increases OCR; however, an innate hypoxic state is associated with low UCP2 levels in this phenotype. In contrast, under normal glucose conditions, … Read more

Given the relatively high level of coexistence, a nonlinear model is more suitable for mutual exclusion than a linear model. Based on mutual exclusion, negative markers were identified for CD4+ cytotoxic T cells, particularly CD126. However, according to FACS analysis, CD28 is the most effective cell surface negative marker. ABSTRACT CD4 cytotoxic T lymphocytes (CTLs) … Read more

The immunoglobulin (Ig) domain exon of human NKp30 contains internal splice sites. A unique intraexonic splicing mechanism produces a short Ig domain that lacks 25 residues but maintains the Ig-fold structure and is expressed on the cell surface. Unlike full-length NKp30, the short version (NKp30-S) does not bind the cancer cell ligand B7H6. ABSTRACT The … 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

European Journal of Immunology, Volume 56, Issue 6, June 2026.

Autofluorescence in liver tissue is heterogeneous and dynamically altered during metabolic liver disease, complicating spectral flow cytometry analysis. We provide a structured framework for identifying and handling condition-dependent autofluorescence, demonstrating that inadequate autofluorescence correction biases macrophage quantification and subset resolution in complex liver samples. ABSTRACT Autofluorescence (AF) in biological tissues arises from the natural emission … Read more

An isolation protocol for plasma cells (PC) from the chicken Harderian gland (HG) was established, and analyses of PCs revealed a FSChigh/CD45med/sIgpos/CD57pos/CXCR4high/TACIlow phenotype. Presence of CXCL12 and BAFF around HG PCs suggests a contribution of CXCL12–CXCR4 and BAFF–TACI to PC localization and survival. ABSTRACT Due to fundamental differences in B cell development between birds and … Read more

We investigated differences in peptide repertoire when β2-microglobulin is fused to the HLA-I heavy chain. We observed: (1) that immunopeptidomes changed in this condition, (2) an overall increased median IC50 of the entire peptide repertoire, and (3) a reduced presentation of cancer-specific epitopes with a strong predicted binding affinity for HLA-I. ABSTRACT β2-Microglobulin (β2m) is … Read more

Our study reveals that STING activation in dendritic cells using cGAMP-VLP enhances CD8+ T cell recognition of live tumor cells by inducing type I interferon-dependent upregulation of MHC-I on tumor cells in vitro. In vivo, cGAMP-VLP boosts antitumor immunity even in cGAS-deficient tumors, thereby improving the efficacy of immune checkpoint blockade. These findings uncover a … Read more

High-dimensional imaging mass cytometry reveals diverse macrophage populations in human dorsal root ganglia (DRG). Microglia-like cells, characterized by markers such as P2RY12, SLC2A5, and TMEM119, localize near neuronal structures, whereas other myeloid subsets are found in interstitial regions. Spatial analysis reveals distinct localization patterns within the DRG. ABSTRACT The human dorsal root ganglia (DRG) are … Read more

This study shows that loss of sialylation in CT26 cells reduces peritoneal tumor burden, correlating with a lower peritoneal cancer index score. These tumors exhibited increased immune infiltration with prominent alterations in the myeloid compartment and immune cell correlations unique to desialylated tumors, indicating profound reshaping of antitumor immunity. ABSTRACT Colorectal cancer (CRC) patients are … Read more

YB-1 is essential for invariant NKT cell development, integrating TCR, co-stimulatory, and IL-15 signaling to control maturation, subset differentiation, and survival. Its loss at the double-positive thymocyte stage causes ∼80% iNKT cell depletion, maturation arrest, impaired cytokine production, and increased apoptosis. ABSTRACT Y-box binding protein 1 (YB-1) is a multifunctional RNA- and DNA-binding protein with … Read more

The A allele of the intronic SNP rs80262450 in the PTPN2 gene favors the expression of the splicing isoform PTPN2.4. This cytoplasmic isoform enhances TNF-α production in myeloid cells, thereby contributing to intestinal inflammation. These findings identify PTPN2.4 as a key pathogenic regulator and potential therapeutic target for inflammatory bowel disease. ABSTRACT Genome-wide association studies … Read more

Hypoxia activates the HIF complex (HIF-1α, HIF-1β, HIF-2α) to induce AID expression in B cells independently of cytokine signaling. However, hypoxia alone is insufficient to trigger class switch recombination (CSR), which additionally requires cytokine-driven chromatin accessibility, highlighting a mechanistic uncoupling between AID induction and functional antibody diversification. ABSTRACT Hypoxia has been shown to shape the … Read more

This study showed dysregulated αβ T cell homeostasis with ongoing T cell activation and low-grade inflammation in 5-12-year-old CHD children who underwent early-life cardiac surgery with thymectomy, characterized by reduced naïve T cells and increased memory/effector and senescent-like T cells. There was also higher expression of inhibitory receptors on effector T cells and elevated suppressive … Read more

Genetic and epidemiological studies have together identified hundreds of risk factors for MS, but we know relatively little about the mechanisms through which these cause disease. In this review, we explore a new generation of studies that are integrating genetics and environment to uncover disease mechanisms. Progress toward novel therapeutics is likely to come from … Read more

Nur77 is associated with a TCF-1+ memory-like, polyfunctional profile in virus-specific human CD8+ T cells across acute-resolved, vaccinated, and chronic viral infections, and its pharmacologic modulation in vitro enhances the functionality of dysfunctional HIV- and HBV-specific CD8+ T cells in chronic co-infections. ABSTRACT Human CD8+ T cells undergo significant metabolic and transcriptional shifts during activation … Read more

The evolving landscape of transcriptomic technologies tailored for neutrophil research. ABSTRACT Tumor neutrophils exhibit marked phenotypic plasticity and can play dual roles in tumor biology, encompassing both tumor-promoting and tumor-suppressive activities. Single-cell RNA sequencing (scRNA-seq) enables transcriptomic profiling of tumor neutrophils at single-cell resolution, whereas spatial transcriptomics (ST) addresses key limitations of scRNA-seq by preserving … Read more

In the absence of a pre-BCR, a subset of mature B cells that expresses IgH chains with very short, hydrophobic and positively charged H-CDR3 loops is generated. This results in massive clonal expansion and the development of autoreactive plasma cells exhibiting these characteristics. ABSTRACT The immune system is essential for protection against invading pathogens. However, if … Read more

Basal IFN-I acts as a rheostat to fine-tune CD8 T cell anergy. The presence of IFN-I induces a less deep anergic state characterised by greater expansion, residual effector function and plasticity. This favours the accumulation of autoreactive T cells that retain the potential to break tolerance rather than undergoing deletion. Created in BioRender (2026). https://BioRender.com/y0syq8s … Read more

European Journal of Immunology, Volume 56, Issue 5, May 2026.

Integrated overview of host defense and immune evasion in Lyme Borreliosis. Bbsl evades immunity through tick saliva-mediated suppression of innate defenses, TLR2/NOD2-driven cytokine dysregulation, and interference with JAK/STAT and CIITA-dependent antigen presentation. Impaired autophagy skews responses toward pathogenic Th17 activity, while disrupted lymph node architecture, persistent IgM, and defective CD4+ T cell function collectively impair … Read more

Spatial multiomics profiling can reveal how tumor heterogeneity and microenvironment influence ADC efficacy. Combining spatial transcriptomics, proteomics, and AI-based analysis improves the identification of tissue factors influencing therapy response. This integrative approach potentially enables prediction of response, resistance, and optimized patient selection, which we review here. ABSTRACT Antibody–drug conjugates (ADCs) have transformed the therapeutic landscape … Read more

IC-mediated inflammatory response—the NLRP3 inflammasome activation, cytokine secretion, and antigen presentation depend on SYK signalling pathways in primary murine microglia. ABSTRACT Viral infections might trigger systemic inflammatory responses characterised by inflammasome activation and cytokine release, driven by immune complex (IC) formation, but the precise mechanism remains unknown. The NLRP3 inflammasome is a vital component of … 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

An attenuated live vaccine (OTS-300) expressing the XBB.1.5 Spike provided rapid and complete protection against homologous challenge in the hamster model, accompanied by fast systemic and mucosal antibody responses and markedly reduced transmission compared with XBB.1.5 mRNA vaccination. Therefore, vaccination with the OTS LAV platform may help to disrupt transmission chains. ABSTRACT The emergence of … Read more

We previously showed that primary differentiation of naïve T cells is dependent on IRF4. Now we show that maintenance of already differentiated conventional and pathogenic Th17 cells is also dependent on IRF4.

ADAR1 expression increase during monocyte-to-macrophage differentiation via an alternative transcription start site. Isoform-specific ADAR1 activity governs key macrophage functions, including efferocytosis, endocytosis, lipid metabolism, and proliferation. Moreover, ADAR1 in macrophages responds to different metabolic states and buffers lipotoxicity under high metabolic load. Vectors obtained from https://BioRender.com. ABSTRACT Adenosine deaminase acting on RNA 1 (ADAR1) regulates … Read more

Compared with IgG+ and IgM+ memory B cells, IgA+ memory B cells displayed distinct phenotypical markers: PD-L1, GPR183, CCR9, CCR10, α4β7, CD11b. A particular transcriptomic signature, with RUNX2, ARHGEF10L, XYLT1, TRPS1, and CHL1 upregulation, characterized the IgA+ memory B cell population, whereas miR4432HG was a marker of IgG+ memory B cells. ABSTRACT IgA is the … Read more

By comparing various brain tumors, we identified a CX3CR1+ Siglec10+ double-positive macrophage subpopulation specifically enriched in highly malignant Glioblastomas (GBMs), wherein they accumulated in metabolically active tumor areas. Thus, they potentially serve as a diagnostic indicator population for GBMs and as targets of future GBM-specific treatment strategies. ABSTRACT Glioblastoma (GBM) is one of the most … Read more

ABSTRACT EXPRESSION OF CONCERN: M. Barel, M. Balbo, M. Le Romancer and R. Frade, “Activation of Epstein-Barr Virus/C3d Receptor (gp140, CR2, CD21) on Human Cell Surface Triggers pp60src and Akt-GSK3 Activities Upstream and Downstream to PI 3-Kinase, Respectively,” European Journal of Immunology 33, no. 9 (2003): 2557–2566, https://doi.org/10.1002/eji.200324059. This Expression of Concern is for the … Read more

Constitutive interferon (IFN) production is regulated by microbiota and essential for optimal immune responses. Here, we demonstrate that expression of the glycoprotein of LCM virus upregulates constitutive IFN-β levels and IFN-stimulated genes (ISGs) in transgenic mice. Moreover, it increased self-antigen-driven memory-phenotype CD4 T cells and effector regulatory CD4 T cells. ABSTRACT Besides the strong Type … Read more

Through the lens of spatial transcriptomics and associated tools, novel immune niche constituents can now be resolved. Drawing on gut and tumor contexts, we propose a framework to define immune niches and integrate clonal dynamics, aiming to advance niche-directed therapies toward precise, context-specific immune modulation. ABSTRACT Spatial transcriptomics allows for the investigation of complex cellular … Read more

Wharton’s jelly-derived mesenchymal stromal cells isolated from umbilical cord were used to recreate a human stromal environment for B-cell development in vitro. In co-culture, CD34+ hematopoietic progenitors from bone marrow or cord blood differentiated into mature IgM-expressing B cells by day 11, while the Nalm-16 B-ALL cell line showed rapid IgM expression as early as … Read more

Human memory Th cells were separated into Tcm (CD45RO+ CD62L+) and Tem (CD45RO+ CD62L−). Nicotine preferentially suppressed Th1-, Th2-, Th17-, and Tfh-associated programs in Tcm via an α7nAChR-dependent mechanism, with minimal effect in Tem. ABSTRACT Memory T helper (Th) cells sustain protective recall responses but can also drive chronic inflammation, necessitating precise regulation of their … Read more

Nectin-4 is a tumour-specific antigen that interacts selectively with the immune receptor TIGIT, resulting in inhibition of NK-cell cytotoxicity. We have explored the molecular and structural basis of this interaction and leveraged the information for structure-guided engineering of a TIGIT mutant exhibiting higher interaction affinity with nectin-4 and weaker binding to nectin-2 and PVR. The … Read more

To enable the analysis of B cell and T cell immune responses in mouse lymph nodes, spleen, and bone marrow, including different B cell and T cell subsets and their activation status, as well as the antigen-reactivity and isotype of B cells, a novel 31-parameter spectral flow cytometry panel was developed.

Thymic Stromal Lymphopoietin (TSLP) regulates the skin microenvironment during type 2 inflammation. Epidermal APCs, Langerhans cells (LCs), might be the target of TSLP, but whether LCs express CD127 needed for TSLP signaling has been unclear. We found that LCs express both receptor chains needed by TSLP (CD127 and TSLPR) and upregulate the TSLPR upon Calcipotriol … Read more

Current plasma cell–targeting therapies lack antigen specificity. Using an antibody-mediated cytotoxicity engager (ACE) targeting the α-subunit of the extracellular domain of the human acetylcholine receptor (hAChR αECD), we selectively depleted pathogenic antibody-secreting cells in a myasthenia gravis model, reducing autoantibody titers and disease severity while preserving nonspecific antibody-secreting cells and humoral immunity. ABSTRACT Myasthenia gravis … Read more

In a neonatal mouse model of E. coli sepsis, depleting neonatal neutrophilic cells (NNC) increased mortality and systemic inflammation. The bacterial load increased slightly, and the immune cell populations remained unchanged. These findings suggest that NNC may play a role in controlling inflammation and protecting neonates from lethal sepsis. ABSTRACT Neonates are particularly susceptible to … Read more

Lymphatic endothelial cells at the cribriform plate and in brain-draining cervical lymph nodes express PD-L1 during autoimmune encephalitis. Unexpectedly, deletion of lymphatic PD-L1 expression ameliorates disease symptoms and is associated with increased brain infiltration of regulatory CD8+ Foxp3+ T cells.

Anti-cN1A autoantibodies are helpful for diagnosing inclusion body myositis (IBM). We have developed an immunofluorescence assay based on the perinuclear accumulation of GFP-cN1A. The analysis of patient sera indicated that this assay shows a higher sensitivity for anti-cN1A in IBM compared to alternative assays, without loss of specificity.

A preclinical model of TLR7-agonist-induced psoriasis develops insulin resistance by 3 weeks. Development of this psoriasis-associated insulin resistance can be prevented by systemic blockade of type I interferon signaling. ABSTRACT Psoriasis is a cutaneous autoimmune disease with worldwide prevalence. In situ activation of skin-infiltrating plasmacytoid dendritic cells (pDCs) leading to local induction of type I … Read more

Irgm1 regulates inflammatory disease by modulating leukocyte responses including those of T cells. In CD4+ T cells, Irgm1 functions in a cell-intrinsic manner. However, in CD8+ T cells, Irgm1 restrains cytokine production and cell death in a cell-extrinsic manner by controlling type I interferon production from hematopoietic and other sources. ABSTRACT Immunity-related GTPases (IRGs) are … Read more

Long-COVID or post-acute sequelae of COVID-19 syndrome (PASC) patients with previous severe COVID-19 ICU history prior vaccination display sustained significant changes in their immune profile at both the cellular and the inflammatory level, revealing signatures of persistent inflammation and endothelial injury. ABSTRACT SARS-CoV-2 infection can lead to persistent symptoms (i.e., long/post-COVID), especially in unvaccinated individuals. … Read more

Inhaled pretreatment of mouse lungs with immunomodulatory Pam2ODN results in lung epithelial cell epigenetic reprogramming that is associated with attenuation of house dust mite extract (HDM)-induced cDC2s and moDCs expansion in the lung, causing tolerance against HDM sensitization and restricting Th2-cell-induced airway eosinophilic allergic inflammation. ABSTRACT Prophylactic inhalation of the synergistic agents ODN M362 and … 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

European Journal of Immunology, Volume 56, Issue 4, April 2026.

Investigation of IFN signaling in cultured skin fibroblasts from patients with genetically confirmed mitochondrial diseases of diverse origins revealed that altered IFN signaling is an inconsistent feature of these disorders. Cytosolic accumulation of mtDNA and mtRNA was variably detected and showed little correlation with ISG scores. ABSTRACT Mitochondria have long been known to be involved … Read more

This review highlights how memory-phenotype CD8+ T lymphocytes (TMP) develop in immunologically naive hosts in the absence of non-self-antigens (Ag). We discuss the current understanding and controversies on the origin, maintenance and functions of the main populations recognized as TMP, in comparison to naive (TN) and Ag-specific true memory T cells (TTM). ABSTRACT Conventional or … Read more

Oleic acid enhances Treg cell differentiation by inducing autophagy via AMPK activation and mTORC1 inhibition. In DSS-induced colitis, oleic acid treatment expands colonic Tregs, reduces inflammatory cytokines, and ameliorates intestinal pathology. ABSTRACT Oleic acid (OA), a monounsaturated fatty acid (FA) prevalent in olive oil and key component of Mediterranean diet, exhibits anti-inflammatory effects in ulcerative … Read more

Systems immunology provides a transformative framework for decoding human immune complexity. This review evaluates high-throughput technologies and provides a roadmap for navigating analytical challenges—such as batch effects and interindividual heterogeneity—to successfully translate multimodal data into meaningful biological insights. ABSTRACT The human immune system is a highly complex, dynamic, and heterogeneous network shaped by genetic, environmental, … Read more

Mice with natural microbiota show expected ageing spleen trends: naïve T cell loss with effector-memory expansion, mature B cell shifts, Gzmk + CD8+ T cell heterogeneity, diminished NK cytotoxicity and pro-inflammatory macrophages. Chronic stress modestly counteracted these age-related changes. Splenocyte transcriptomic atlas reveals reproducible compositional shifts and defines conserved cell-type-specific ageing signatures. ABSTRACT Immune ageing … Read more

Mouse Qa1b-restricted T cells show promiscuous requirements for positive selection. Using in vivo tetramer enrichment, in vitro APC engineering, and in vitro thymocyte stimulation, we demonstrate that a Qa1b-restricted T cell population can be selected by both Qa1b and H2-T11, and depends on non-cognate CD8-MHC I binding. ABSTRACT MHC-E-restricted CD8 T cells are emerging as … Read more

Characterization of the early antigen-specific B cell response post-SARS-CoV-2 vaccination reveals novel activated B cell clusters, showing different phenotypes and contraction dynamics. Some short-lived activated B cells expressed both CD71 and the extrafollicular marker CD11c. These results advance our understanding of B-cell differentiation regulation and biomarker potential. ABSTRACT In humans, the stages and dynamics of … Read more

We performed combined proteome and transcriptome analysis of human isotype-defined B cell subsets. IgG4-switched B cells were most distinct from naive B cells in terms of mRNA as well as protein expression profiles. SDR16C5 was identified as uniquely upregulated in IgG4-switched B cells. ABSTRACT Antibodies produced by B cells aid in the recognition and clearance … Read more

Immunoglobulin products derived from pooled global plasma reflect population-level antiviral immunity. Analysis of batches from 2017 to 2023 reveals pandemic-driven shifts in viral antibody profiles and a concurrent rise in autoantibodies, notably against TRIM21/Ro52, highlighting links between SARS-CoV-2, immunity debt, and autoimmunity. ABSTRACT Immunoglobulin (Ig) replacement therapy is commonly used to prevent infections in individuals … Read more

Changes in adaptive immunity in autoimmune diseases and aging exhibit both shared and distinct alterations in immune cell compartments. Immune vulnerability is influenced by these alterations, which affect infection susceptibility and vaccination response in these clinically different but immunologically related conditions. ABSTRACT Immunologically vulnerable populations (IVP) are particularly at risk of infection due to dysregulated … Read more

This is an update to the Guidelines for the Use of Flow Cytometry and Cell Sorting in Immunological Studies (Third Edition), Chapter 12C, by Cossarizza et al. A 38-marker full-spectrum flow cytometry panel enabling high-resolution profiling of human γδ T cells across blood and lymphoid tissues, including robust identification of rare, tissue-adapted subsets.

Allergic reaction-derived IL-33 activates ST2 to trigger selective eosinophil activation. IL-33 in a type 2 immune response environment induces biogenesis of lipid bodies in eosinophils, platforms for the generation of lipid mediators, and selectively triggers LTC4 production. ABSTRACT Like pieces of a puzzle, IL-33, eosinophils, and cysteinyl leukotrienes seem to come together and orchestrate allergic … 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

European Journal of Immunology, Volume 56, Issue 3, March 2026.

The CD40-CD40L pathway is often dysregulated in B-cell-driven autoimmune diseases, making the development of CD40L inhibitors a promising therapeutic approach in managing autoimmune responses. We developed an inhibitory anti-CD40L Fab fragment, Fab20, and demonstrated that Fab20 effectively suppresses B-cell proliferation, differentiation, and antibody production in vitro. Made with Biorender. ABSTRACT Dysregulation of the CD40-CD40L axis … Read more

We developed a 50-plex imaging protocol using the MACSima platform to characterize the microarchitecture of germinal centers in secondary lymphoid tissues. This workflow combines tissue processing, automated cyclic imaging, image preprocessing, and a new analysis method that detects morphological changes in irregularly shaped stromal cells.

Human lamina propia mononuclear cells (LPMC) were isolated from intestinal biopsies and resections, as well as peripheral blood mononuclear cells (PBMC) from blood. Using flow cytometry approaches, we characterized cDC subsets and assessed their functional capacity through T-cell coculture assays (after isolation of the different subsets of cDC using sorter cytometry). This approach enabled a … Read more

1. Normal state: T-cell-endogenous IL-6 stabilizes IL6R and promotes STAT3 activation, functional Th17 differentiation with resistance to immune suppression. 2. Il6-KO: Loss of T-cell endogenous IL-6 destabilizes IL6R expression, leading to suboptimal Th17 and greater susceptibility to suppression, despite availability of exogenous IL-6. 3. IL-21 bypasses the requirement for endogenous IL-6 by restoring STAT3 signaling … Read more

EBV latent and lytic genes uniquely contribute to Multiple Sclerosis development by various immunopathogenic mechanisms in susceptible hosts. Briefly, EBV infection shapes the B-cell repertoire and promotes the oligoclonal expansion and subsequent CNS infiltration of T-bet+CXCR3+ B cells, resulting in a cascade of immune dysregulation, CNS inflammation, and autoreactive T cell stimulation. Created in BioRender. … Read more

Chemical library screening identified lomitapide as a novel mast cell (MC) regulatory agent. Lomitapide selectively inhibits IgE/Ag- or phorbol 12-myristate 13-acetate (PMA)/ionomycin-mediated MC degranulation by altering plasma membrane dynamics, including endocytosis and membrane fusion. ABSTRACT Allergic diseases are a global health concern, and new molecular insights and therapeutic agents are necessary to support future research … Read more

Using an in vitro PBMC assay, we found that the addition of exogenous IL-21 enhances the cytotoxic potential of MAIT cells activated by 5-OP-RU. IL-21 induces STAT phosphorylation and provides co-stimulation to TCR-activated MAIT cells, selectively augmenting granzyme B and perforin expression without enhancing interferon-gamma or TNF production at 6 h. ABSTRACT Mucosal-associated invariant T (MAIT) … Read more

FoxP3, a lineage-defining transcription factor, defines mammalian Tregs together with antibodies against CD25, GITR, and CTLA-4. No valid chicken anti-FoxP3 or surface CTLA-4 antibodies are available to date. Given current experimental tools, the study proposes CD4+CD25+GITR+ as a practical panel for phenotypic characterization and sorting of viable chicken Tregs. ABSTRACT Regulatory T cells (Tregs) are … Read more

Group 2 innate lymphoid cells (ILC2s) are tissue-resident cells regulated by diverse signals often emanating from surrounding nonhematopoietic cells at barrier surfaces. Their effector cytokines determine tissue homeostasis at steady state and during type 2 immunity in allergies or worm infections. Redundant and unique functions of ILC2s and T cells are assessed in this context. … Read more

Sex-specific pre-vaccination immune landscapes associated with effective BCG vaccine responses. Male high responders exhibit a monocyte-enriched, pro-inflammatory innate immune profile, whereas female high responders display immune signatures associated with enhanced adaptive immune responses. ABSTRACT Vaccines are a cornerstone of global public health, but their efficacy can vary significantly among individuals. Bacille Calmette-Guérin (BCG) vaccine against … Read more

We report a novel case of complete complement Factor B deficiency revealed by invasive meningococcal disease. Using combined functional and genetic analyses, we demonstrate that loss of Factor B abolishes alternative pathway activity despite detectable protein levels. These findings provide a mechanistic framework relevant to complement diagnostics and to the clinical use of Factor B … Read more

We developed murine CMV-based viral vectors expressing SARS-CoV-2 spike antigen and compared immune response following intraperitoneal and intranasal delivery. Route of vaccine administration shaped antibody and CD8+ T cell response magnitude, kinetics, and tissue residency, highlighting the potential of CMV vectors for induction of protective lung immunity. Created in https://BioRender.com. ABSTRACT Current COVID-19 vaccines face … Read more

GPA33 identifies stable human regulatory T cells suitable for therapeutic use. GPA33+ Treg subsets expand efficiently, maintain high FOXP3+Helios+ expression, and lack production of IL-2, IFNγ, and IL-17A. GPA33, alone or combined with TIGIT, also enables robust post-expansion isolation of pure, stable Treg cells for adoptive cell therapy. ABSTRACT Adoptive cell therapy (ACT) with regulatory … Read more

CD83 and UBL3 are regulators of MHCII surface expression; however, only CD83 has a known role in regulating CD4+ T cell selection. This paper describes a role for UBL3 in regulating MHC II expression on thymic epithelium in a CD83-deficient context, leading to alterations in CD4+ T cell positive selection. ABSTRACT CD83 is critical for … Read more

LCMV-infected Znfx1-deficient mice develop hemophagocytic lymphohistiocytosis (HLH)-like immune dysregulation, mirroring key aspects of the immunopathology observed in ZNFX1-deficient patients. ABSTRACT Hemophagocytic lymphohistiocytosis (HLH) is a severe inflammatory syndrome characterized by persistent activation of lymphocytes and macrophages. Recently, deleterious autosomal recessive mutations in ZNFX1 were reported to predispose pediatric patients to HLH-like disease upon viral trigger. … Read more

A deeper understanding of the natural killer cell gene expression regulation driving NK cell maturation and cytotoxicity could provide critical insights into optimizing NK therapies. Our findings reveal novel enhancers governing NK cell genes for NCAM1/CD56 and cis-regulation for KIR receptors and clarify existing models of NK cell cis-accessibility regulation. ABSTRACT Owing to their immunoprotective … Read more

European Journal of Immunology, Volume 56, Issue 2, February 2026.

Mechanism of action of the intestinal microbiota on CNS autoimmune diseases. Environmental factors shape gut microbiota composition; dysbiosis alters microbial metabolites and antigenic signals. These modulate innate and adaptive immunity, affect barrier integrity, and influence CNS-resident cells such as microglia and astrocytes, contributing to immune-mediated CNS pathology. Multiple sclerosis (MS), neuromyelitis optica spectrum disorder (NMOSD), … Read more

Phagocytosis of yeast activates recruitment of proteases and trafficking factors from the secretory and endosomal pathways to the IRAP compartment and subsequently phagosomes, promoting cross-presentation. In the absence of Sec22b, IRAP endosome and phagosome maturation to late endosomes is accelerated. ABSTRACT MHC class I (MHC-I) cross-presentation involves final proteolytic peptide processing by the endosomal insulin-regulated … Read more

We identified RANK (TNFRSF11a) expression in human thymic FOXP3+ Tregs, revealing a previously unknown role for the RANK-RANKL axis in human tTreg development. We show that IL-2 and IL-15 can drive RANK expression in CD4+ tTregs, which in turn may modulate their maturation and proliferation within the thymic environment. Created in BioRender. Biorender, I. (2026) … 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

Specific pro-inflammatory cytokines destabilize CD8+ Tregs, altering their phenotype and reducing FOXP3 expression. Enforced FOXP3 expression, or the upregulation of its molecular regulators, partially protects CD8+ Tregs from inflammatory disruption, restoring their phenotype and maintaining suppressive function under inflammatory conditions. ABSTRACT Cell therapy using regulatory T cells (Tregs) holds therapeutic promise in immune-mediated diseases, but … Read more

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

European Journal of Immunology, Volume 56, Issue 1, January 2026.

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

European Journal of Immunology, Volume 56, Issue 1, January 2026.

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

European Journal of Immunology, Volume 56, Issue 1, January 2026.

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