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
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
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
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
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
The increased lactate secretion by B cells from people with obesity and aging is a stimulus for pathogenic autoimmune anti-dsDNA antibodies. The effects of lactate are mediated by phosphorylated signal transducer and activator of transcription 3 (p-STAT3) and inhibited by a neutralizing antibody that blocks the lactate transporter SLC5A12, responsible for lactate uptake and activation … Read more
Picture-book compartmentalization makes tonsillar tissue an ideal model to study spatial immunology. Using single-molecule imaging (SMI) of whole-tissue sections, we showcase many an alternative view on tissue composition and architecture that these data and concomitant analyses provide—at the level of single cells, cellular neighborhoods, and anatomical units such as germinal centers and epithelial substructures. ABSTRACT The … Read more
SARS-CoV-2 mRNA vaccination triggers bystander activation of B cells, transiently increasing antibody levels after the first vaccination against influenza, RSV, and tetanus. Reactivation of B cell responses also occurred, where (CD11c+) MBC and DN3 are expanded after SARS-CoV-2 mRNA vaccination, independent of antigen exposure. ABSTRACT After antigen encounter, long-lived antibody-secreting cells (ASC) secrete high-affinity circulating … Read more
Synovial tissue macrophages are essential coordinators of joint homeostasis and inflammatory responses in rheumatoid arthritis. Here, we highlight recent advances that have enabled a deeper characterization of synovial tissue macrophages and their distinct phenotypes and functions in health and disease. ABSTRACT Synovial tissue macrophages are critical orchestrators in the pathogenesis of rheumatoid arthritis, comprising a … Read more
Our cover features images related to flow cytometry techniques widely used for analysis of function and phenotypes of major human and murine immune cell subsets, superimposed on a multidimensional immune cell population scatter plot. These images are taken from the third edition of EJI’s Flow Cytometry Guidelines by Cossarizza et al., a comprehensive resource prepared … Read more
The C-terminal of TSP-1 senses cell contact, which triggers N-terminal cleavage by urokinase, adhesion, and cytoplasmic spreading in T cells and platelets. In contrast, full-length TSP-1 induces the development of polar cell shape and migration in T cells 2D and 3D; polar cell shape 2D, independent of its receptor LRP1, and polar cell shape 3D … Read more
This review summarizes emerging spatially resolved multi-omics approaches revealing organized cell–cell interactions in skeletal muscle and brain inflammation. These tools uncover radiating molecular programs and niche-specific immunopathology that shape cellular reactivity and vulnerability. ABSTRACT Spatial omics technologies enable high-resolution mapping of transcriptomic, proteomic, and metabolic profiles within intact tissues, revealing how immune, stromal, and parenchymal … Read more
CCR7-mediated chemokine signaling regulates the medullary migration of thymocytes to establish self-tolerance. By comparing the thymic phenotype of Ccl21b-KO mice with that of Ccl21a-KO mice, we show that Ccl21a plays a predominant role compared with Ccl21b among CCR7 ligands in the thymus. ABSTRACT Self-tolerance in T cells is a vital self-defense strategy for mammals to … Read more
HLDA Workshops were established 40 years ago to develop a standardized CD molecule nomenclature for leukocyte cell-surface molecules by comparing monoclonal antibodies (mAbs) produced by different laboratories and companies. The HLDA11 Workshop focused on validating G-protein-coupled receptors (GPCRs) targeting mAbs and assessing cell-type-specific expression patterns in leukocytes. ABSTRACT Monoclonal antibodies (mAbs) targeting cell-surface molecules are … Read more
The RNA-binding ROQUIN paralogs are critical immune regulators. We demonstrate that mast cell-specific deficiency for ROQUIN-1 and ROQUIN-2 in mice leads to loss of mast cells in serous cavities. ROQUIN-1 and 2 ablation does not affect mast cell degranulation or proinflammatory cytokine secretion, although they regulate many mRNAs directly or indirectly. ABSTRACT Mast cells are … Read more
SARS-CoV-2 vaccination in rheumatoid arthritis leads to the development of CD4+ and CD8+ spike-specific T cell memory, regardless of immunosuppressive therapies, and the number of vaccine injections. CD4−CD8− double-negative (DN) T cells responded to SARS-CoV-2 peptide epitopes and differentiated into CD8+ cytotoxic T cells after stimulation, suggesting a role in exacerbating the inflammation in RA … Read more
Antibody feedback dynamically shapes the selective landscape for GC B-cells, acting as a driving force of Darwinian-like affinity maturation of B-cell receptors (A). It also balances epitope usage, leading to equal competition among B cell clones specific for different epitopes and allowing the emergence of clones specific for new epitopes (B). ABSTRACT Antibody feedback in … Read more
Early B cell activation requires both FcµR and IgM-mediated complement signaling, which together drive initial clonal expansion, class-switch recombination, germinal center (GC) entry, and plasma cell differentiation. During the GC reaction, IgM BCR-mediated complement activation, but not FcµR, supports GC B cell survival, proliferation, and affinity maturation. ABSTRACT Secretory IgM plays a pivotal role in … Read more
Murine allergy model outcomes differ by sensitization route, allergen type, and mouse strain, influencing mechanisms such as IgE and mast cell involvement and the therapeutic relevance of each model. Understanding how experimental parameters shape outcomes is essential for selecting appropriate models and effectively translating findings to clinical applications. ABSTRACT Immunoglobulin E (IgE)–mediated immediate hypersensitivity reactions … Read more
Staphylococcal enterotoxin A (SEA) alters monocyte differentiation and function, while preserving T cell stimulatory capacity. SEA-primed macrophages downregulate antigen-presenting markers yet drive heightened T-cell proliferation and IFN-γ secretion. These findings reveal mechanisms of SEA-mediated immune modulation and superantigen-driven inflammation. ABSTRACT Staphylococcal enterotoxins (SE) crosslink the MHC-II on antigen-presenting cells (APC) with the T-cell receptor, inducing … Read more
Severe COVID-19 is associated with hyperinflammation driven by anti-spike IgG immune complexes (ICs) contributing to macrophage hyperactivation, thrombosis, and tissue damage. This study shows that anti-spike IgG ICs induce rapid metabolic reprogramming, specifically glycolysis, fatty acid synthesis, and the pentose phosphate pathway, which is essential for the inflammatory response. Targeting these metabolic pathways may offer … Read more
Unannotated splicing and translation of non-canonical open reading frames generate a diverse repertoire of cryptic proteins. Most are rapidly degraded, rendering them possible MHC-I substrates. Yet, a subpopulation can adopt stable structures and impart advantageous functions. This dichotomy both expands the antigen landscape and provides a framework for protein evolution. ABSTRACT The widespread translation of … Read more
This is an update to the Guidelines for the use of flow cytometry and cell sorting in immunological studies (third edition), Chapter 3: 12C, by Cossarizza et al. Administration of anti-ARTC2 nanobody(S+16a) prevents cell death during tissue processing. We demonstrate that the phenotype of CD44midTreg is significantly impacted, whereas the eTreg phenotype remains stable following … Read more
Here, we show increased MHC class I levels on B cells, classical and intermediate monocytes, and a shift in CD8+ T cells toward a Tc1-skewed, proinflammatory phenotype in the peripheral blood mononuclear cells of people with type 2 diabetes mellitus. ABSTRACT Effective antigen presentation by major histocompatibility complex (MHC) molecules to T cells is crucial … Read more
HCV re-infection is common after spontaneous clearance of the initial infection. In the rare group of super-clearers who clear repeatedly, HCV-specific CD8+ T memory stem cells (TSCM) retain stemness, proliferation, and multipotency, sustaining immune protection. In contrast, clearer chronics lose these properties. TSCM self-renewal underpins durable immunity and should inform vaccine design. ABSTRACT Natural clearance … Read more
Selecting a sensitive test system is crucial to measure IFNα in serum samples. Simoa digital ELISA stands out for its high sensitivity and strong correlation with transcript-based IFN-induced gene (ISG) scores. In SLE, the ISG score is explained by circulating IFNα levels with negligible contribution from IFNβ or IFNγ. Created in BioRender.
Using mass cytometry, we map the heterogeneous activation of the STING pathway at single-cell resolution in cell lines and primary human immune cells and validate them with conventional techniques. ABSTRACT The stimulator of interferon genes (STING) pathway plays a pivotal role in innate immunity, acting as a key sensor of cytosolic DNA to initiate type-I … Read more
We optimised a protocol for mHA-specific Treg (mTreg) selection in an HLA-matched context while defining its phenotype, transcriptional state and function. mTreg were highly activated and exerted specific, HLA class II-, contact-dependent suppression. This protocol can be explored as a highly personalised antigen-specific Treg-based therapy in future clinical trials for cGVHD. ABSTRACT Graft-versus-host disease is … Read more
This review highlights the hierarchical transcriptional networks that govern macrophage specification and function. We describe how lineage-determining, identity-imprinting, and tissue-specific transcription factors coordinate macrophage differentiation and specialization across organs, emphasizing the transcriptional regulation underlying macrophage diversity in health and disease. ABSTRACT Tissue-resident and recruited macrophages are integral to organ development, homeostasis, immunity, and disease pathogenesis. … Read more
The Janus face of group 3 innate lymphoid cells (ILC3s). ILC3s are highly plastic and can adapt their immunoregulatory roles according to the local context, balancing tolerance and activation. Influenced by tissue-specific environmental cues, they can express MHC class II molecules either alone or jointly with costimulatory molecules, therefore presenting acquired antigens for controlling or … Read more
Our cover features images related to flow cytometry techniques widely used for analysis of function and phenotypes of major human and murine immune cell subsets, superimposed on a multidimensional immune cell population scatter plot. These images are taken from the third edition of EJI’s Flow Cytometry Guidelines by Cossarizza et al., a comprehensive resource prepared … Read more
How the immune system of people with diabetes responds to vaccination against respiratory viruses is not well understood. Using activation-induced markers to identify, quantify, and functionally characterize Spike-specific CD4+ and CD8+ T cells after SARS-CoV-2 vaccination, we show defects in T cell memory maintenance and an IL-10 and IL-13-dominated T cell response in people with … Read more
This review highlights recent advances that enable spatially resolved analysis of immunometabolism within tissue microenvironments. Integrating mass spectrometry imaging, vibrational microscopy, and spatial omics reveals how metabolic organization shapes immune function in cancer and other pathologies. ABSTRACT The metabolic programs of immune cells influence their activation, differentiation, and effector functions. While much of immunometabolism has … Read more
How chronic immune stimulations differentially shape CD4⁺ T cell senescence remains unclear. Using high-dimensional mass cytometry and functional profiling, we show that cytomegalovirus (CMV) drives expansion of cytotoxic CD27−CD28− CD4⁺ T cells, whereas rheumatoid arthritis (RA) exerts nonredundant effects by modulating their effector capacity. ABSTRACT Chronic antigen exposure drives CD4⁺ T cell senescence, yet how … Read more
Fibroblastic reticular cells (FRCs) in lymph nodes contribute to peripheral tolerance via MHC-class-II-mediated antigen presentation. Using scRNAseq and protein analysis, we identify BST1+CD200+ FRCs, including the mature T cell-zone FRCs, as key MHC-class-II expressing subsets in mice and humans, highlighting their potential role in immune regulation. ABSTRACT Autoimmunity can be initiated by autoreactive T cells … Read more
CD8+CD69− memory T cells (Schneider Revueltas et al.) were identified to reside in bone marrow besides canonical CD8+CD69+ tissue-resident memory T cells (TRM). In addition, CD4+CD69+ Tr1-like cells (Pulvirenti et al.) were preferentially found in bone marrow. Together, these findings illustrate diversity in the T cell subsets that reside long-term within the bone marrow. ABSTRACT Recent studies … Read more
Proposed mechanism underlying the repression of ZFP36 and induction of ZFP36L1 by calcineurin. ELK-1 is activated by stimuli and promotes the transcription of Zfp36. Calcineurin dephosphorylates active ELK-1 to inhibit its positive effect on Zfp36 transcription, while promoting NFAT-mediated Zfp36l1 transcription. ABSTRACT CD8+ T cells target infected or malignant cells via the production of pro-inflammatory … Read more
Prostaglandin E2 (PGE2) signaling through E-prostanoid receptors (EP) 2 and 4 induces a distinct human macrophage phenotype and affects their functions. Targeting the PGE2-EP2/4 axis in macrophages with soluble or nanoparticle-encapsulated EP2/4 antagonists counteracts the PGE2-induced effect in a 2D and 3D tumor microenvironment using patient-derived tumor organoids. ABSTRACT Prostaglandin E2 (PGE2) is one important … Read more
Innate lymphoid cells (ILCs) have emerged as critical regulators of immune defense, tissue repair, and metabolic homeostasis. By integrating environmental cues, they orchestrate tissue-specific metabolic adaptation. This review discusses ILC functions in adult energy regulation and proposes that neonatal ILCs play essential roles in postnatal metabolic and tissue maturation. ABSTRACT In the almost two decades … Read more
Our cover features images related to flow cytometry techniques widely used for analysis of function and phenotypes of major human and murine immune cell subsets, superimposed on a multidimensional immune cell population scatter plot. These images are taken from the third edition of EJI’s Flow Cytometry Guidelines by Cossarizza et al., a comprehensive resource prepared … Read more
