European Journal of Immunology最新文献

After antigen encounter, long-lived antibody-secreting cells (ASC) secrete high-affinity circulating antibodies. In addition, memory B cells (MBC) are quickly reactivated upon antigen re-exposure and predominantly generate shorter-lived ASCs. Studies have suggested that MBC can differentiate into ASCs without recognizing their cognate antigen, a process known as “bystander activation”. This antigen-independent reactivation of MBC could help maintain circulating antibody levels, thereby protecting against future infections. To elucidate whether SARS-CoV-2 mRNA vaccination leads to bystander activation of B cells, the dynamics of antibody concentrations against six pathogen-specific antigens not encountered during the sampling period were analyzed over time. Deep profiling of antigen-specific B cell responses was simultaneously performed using multiparameter high-dimensional spectral flow cytometry. Antibody concentrations against tetanus toxoid (TT), respiratory syncytial virus (RSV), and influenza hemagglutinin (HA) unexpectedly increased 6 weeks after the first SARS-CoV-2 vaccination. Deep profiling of B cell differentiation stages demonstrated a short-term increase in influenza-specific IgG+ DN3 B cells, RSV-specific IgG+ CD11c+ activated B cells, and TT-specific IgG+ MBC following vaccination. In this study, we demonstrated at both the antibody and cellular levels that SARS-CoV-2 mRNA vaccination transiently activates distinct early activated B cell compartments directed against influenza HA, RSV, and TT.

Synovial tissue macrophages are critical orchestrators in the pathogenesis of rheumatoid arthritis, comprising a heterogeneous population of subsets. Despite the crucial role of these cells in disease, the relative contribution of specific macrophage subsets in the evolution and perpetuation of inflammation in RA has yet to be fully elucidated. Recent technological advances have allowed for a more detailed examination of synovial tissue macrophages, developmentally, functionally, and spatially. Single-cell technologies, for example, have revealed a spectrum of myeloid subsets existing in the synovium in health and disease, with different phenotypic characteristics and functions. This review will explore recent findings in this area. We will review the ontogeny of tissue macrophages, their metabolic demands, and their crosstalk with other key cell types within the synovium, the key site of pathology and immune dysregulation in RA. The contributions of synovial tissue macrophages in shaping the inflammatory environment in RA will also be reviewed, and conversely, we will touch upon mechanisms by which the local environment influences the development of synovial tissue macrophages. A better understanding of these domains will be crucial to the identification of novel therapeutics targeting macrophages in RA.

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 by flow cytometry and immunology research experts from around the world.

Maternal immune activation (MIA) refers to an immune response triggered in a pregnant mother by infections, inflammation, or other immune challenges that can impact offspring health. We propose aligning MIA within the framework of the developmental origins of health and disease (DOHaD) theory because it has the potential to provide mechanistic evidence for long-term outcomes of fetomaternal crosstalk disruptions. MIA models are created by exposing pregnant animals to immune-activating agents such as inosinic-polycytidylic acid (poly I:C) or lipopolysaccharide (LPS), which mimic viral or bacterial infections, respectively. Next to these acute MIA models, chronic helminth infections during pregnancy have been employed as an additional, more physiological model of infection. MIA models have helped researchers explore how maternal infections during pregnancy may impact the offspring's risk of neurodevelopmental disorders. Emerging evidence suggests that these models have a broader impact on organ development, the immune system, and, consequently, immune-related disorders such as allergies. Our review focuses on evidence derived mainly from mouse models of MIA that have investigated maternal signals, such as cytokines and microbiota, on fetal hematopoiesis, adults' immune cell compartments, including the bone marrow, and their relation to the development of offspring allergies. Where applicable, studies from other species are indicated.

Spatial omics technologies enable high-resolution mapping of transcriptomic, proteomic, and metabolic profiles within intact tissues, revealing how immune, stromal, and parenchymal cells interact in situ during inflammation. Chronic inflammation in skeletal muscle and the central nervous system is spatially organized within defined niches that shape disease progression and therapeutic response. In skeletal muscle, spatial analyses have uncovered fiber-type-specific vulnerability, regenerative trajectories, and immune–stromal crosstalk in disorders such as Duchenne muscular dystrophy and inclusion body myositis. In the central nervous system, these approaches have revealed compartmentalized neuroinflammation in multiple sclerosis, innate immune activation in amyotrophic lateral sclerosis, and immune evasion in glioma. Integration with single-cell gene expression enables inference of cell–cell communication networks and identification of spatial gradients of immune activation and tissue remodeling. Despite major advances, clinical translation remains limited by small cohorts, methodological variability, and insufficient functional validation. As spatial profiling becomes more accessible, standardized, and scalable, it promises to stratify inflammatory disease states, identify tissue-resident immune programs, and guide mechanism-based therapies. Hence, spatial omics provide an unprecedented opportunity to resolve the cellular architecture of inflammation, revealing not only where immune activity occurs, but how it is orchestrated within complex tissue microenvironments.

Self-tolerance in T cells is a vital self-defense strategy for mammals to specifically respond to invading pathogens. During T cell development in the thymus, thymocytes migrate from the cortex to the medulla to sequentially acquire non-self-reactivity and self-tolerance. This cortex-to-medulla migration is regulated by CCR7-mediated chemokine signaling. Previous studies have identified CCL21 but not CCL19 as a functional ligand for this CCR7-dependent migration. CCL21 in the mouse is encoded by multiple genes, including CCL21Ser-encoding Ccl21a and several CCL21Leu-encoding genes, including Ccl21b. The importance of Ccl21a in thymocyte migration has been demonstrated, whereas the role of CCL21Leu-encoding genes remains unclear. By producing mice specifically deficient in Ccl21b, we show that Ccl21b plays little to no role in the cortex-to-medulla migration of developing thymocytes. CCL21Leu-encoding gene transcripts remain detectable even in the absence of Ccl21b, suggesting that Ccl21b is not a major source of CCL21Leu. We further show that the copy number of CCL21Leu-encoding genes is smaller than the currently estimated copy number in a public database. These findings underscore the predominant role of Ccl21a over Ccl21b in the mouse thymus.

Monoclonal antibodies (mAbs) targeting cell-surface molecules are pivotal in biomedical research, diagnostic applications, and biotechnology. Over the past four decades, the CD nomenclature system, established by the Human Leukocyte Differentiation Antigens Workshops and endorsed by the International Union of Immunological Societies (IUIS), has provided a standardized naming convention for both mAbs and the cell surface molecules they target. G protein-coupled receptors (GPCRs) represent the largest family of cell-surface receptors, playing essential roles in both innate and adaptive immune responses. Despite their significance, GPCRs are underrepresented in terms of well-validated mAbs available for flow cytometry and therapeutic applications. At the Eleventh HLDA Workshop (HLDA11), new CD nomenclature has been assigned to thirteen GPCR cell-surface molecules expressed on immune cells: CD198 (CCR8), CD199 (CCR9), CD372 (CCR10), CD373 (CX3CR1), CD374 (XCR1), CD375 (GPR15), CDw376 (GPR26), CD377 (SSTR3), CD378 (C3AR1), CDw379 (FPR2), CD380 (LTB4R), CDw381 (GPR183), and CDw382 (F2RL1). In this article, we introduce the newly established CD nomenclature for mAbs targeting the GPCR family. We detail the quantitative expression profiles of these molecules on various subsets of leukocytes and provide validation data for these mAbs. The implications of these expression profiles are discussed for the potential therapeutic targeting of immune-mediated diseases and cancer.

Staphylococcal enterotoxins (SE) crosslink the MHC-II on antigen-presenting cells (APC) with the T-cell receptor, inducing a polyclonal T-cell response. Although APCs are the initial targets of SE and are critical in shaping subsequent T-cell activation, the effects of SE on APC function remain poorly understood. This study investigates the immunomodulatory effects of staphylococcal enterotoxin A (SEA) on monocytes and their differentiation into monocyte-derived dendritic cells (moDC) or macrophages (MDM). Transcriptomic analyses of human monocytes via RNA sequencing revealed SEA-induced enrichment of gene pathways associated with inflammation, infection, and dermatitis, effects that were amplified in the presence of T cells. Phenotypic and functional characterization showed that SEA-primed monocytes differentiated into MDM with an altered polarization, deviating from classical M1/M2 pathways. SEA-primed MDM exhibited downregulation of key markers, including HLA-DR, CD80, CD86, and PD-L1. Functional assays demonstrated that SEA-primed MDM pushed hyperinflammatory T-cell responses, with significantly enhanced proliferation and IFN-γ secretion. In contrast, following SEA-priming, moDC retained robust antigen-presenting capabilities and displayed enhanced expression of molecules involved in T-cell interactions. These findings provide mechanistic insights into SEA-mediated immune modulation, illustrating how SEA reprograms MDM functions and amplifies proinflammatory T-cell responses. This advances our understanding of superantigen-driven immune interactions, offering a foundation for developing therapeutic strategies to mitigate superantigen-mediated immune conditions.