Search PubMed⌕ Search

SEARCH · Search PubMed

Results for “Lymphoid cells”

Search indexed PubMed citations on genomics, clinical trials, systematic reviews and public health. Explore titles, authors and supplied subject terms, then open the PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 19 recordsLinked to original sources
PubMed2012

The transcription factor GATA-3 controls cell fate and maintenance of type 2 innate lymphoid cells.

Innate lymphoid cells (ILCs) reside at mucosal surfaces and control immunity to intestinal infections. Type 2 innate lymphoid cells (ILC2s) produce cytokines such as IL-5 and IL-13, are required for immune defense against helminth infections, and are involved in the pathogenesis of airway hyperreactivity. Here, we have investigated the role of the transcription factor GATA-3 for ILC2 differentiation and maintenance. We showed that ILC2s and their lineage-specified bone marrow precursors (ILC2Ps), as identified here, were characterized by continuous high expression of GATA-3. Analysis of mice with temporary deletion of GATA-3 in all ILCs showed that GATA-3 was required for the differentiation and maintenance of ILC2s but not for RORγt(+) ILCs. Thus, our data demonstrate that GATA-3 is essential for ILC2 fate decisions and reveal similarities between the transcriptional programs controlling ILC and T helper cell fates.

Animals↗
PubMed2026

Genetic Mutation and Epigenetic Silencing Drive Antigen-Negative Relapse in CD7 CAR T-Treated T-cell Lymphoid Malignancies.

UNLABELLED: CD7 is a promising target for chimeric antigen receptor (CAR) T-cell therapy in T-cell lymphoid malignancies; however, antigen loss-mediated relapse has emerged as a major challenge. In this study, we systematically analyzed the genetic and epigenetic alterations of paired specimens (pretreatment and relapsed) from 10 patients with T-cell lymphoma/leukemia receiving CD7 CAR T cells. Overall, we identified three distinct mechanisms underlying CD7 loss: first, frameshift insertion (patient 4; c.164dupG:p.R55fs) or deletion (patient 7; c.122delG:p.G41Efs*19) resulting in truncation of the CD7 transmembrane domain in two of 10 patients; second, hypermethylation of the CD7 promoter in seven of 10 patients without CD7 mutation; third, simultaneous occurrence of promoter region hypermethylation and multiple in-frame mutations with predicted functional interference in one of 10 patients (patient 2). Collectively, these findings demonstrate that both clonal heterogeneity and epigenetic plasticity drive antigen-negative relapse in T-cell lymphoid malignancies under the selective pressure of CD7 CAR T-cell therapy. SIGNIFICANCE: Understanding mechanisms of antigen-negative relapse is critical for developing effective CD7-targeting CAR-T therapies against T-cell lymphoid malignancies. Our study identifies both genetic truncation mutations and epigenetic silencing as contributors to CD7-negative relapse. Monitoring and preventing these events is warranted to improve treatment outcomes.

Humans↗
PubMed2018

E3 Ligase VHL Promotes Group 2 Innate Lymphoid Cell Maturation and Function via Glycolysis Inhibition and Induction of Interleukin-33 Receptor.

Group 2 innate lymphoid cells (ILC2s) are a specialized subset of lymphoid effector cells that are critically involved in allergic responses; however, the mechanisms of their regulation remain unclear. We report that conditional deletion of the E3 ubiquitin ligase VHL in innate lymphoid progenitors minimally affected early-stage bone marrow ILC2s but caused a selective and intrinsic decrease in mature ILC2 numbers in peripheral non-lymphoid tissues, resulting in reduced type 2 immune responses. VHL deficiency caused the accumulation of hypoxia-inducible factor 1α (HIF1α) and attenuated interleukin-33 (IL-33) receptor ST2 expression, which was rectified by HIF1α ablation or inhibition. HIF1α-driven expression of the glycolytic enzyme pyruvate kinase M2 downmodulated ST2 expression via epigenetic modification and inhibited IL-33-induced ILC2 development. Our study indicates that the VHL-HIF-glycolysis axis is essential for the late-stage maturation and function of ILC2s via targeting IL-33-ST2 pathway.

Animals↗
PubMed2015

Transcriptional programs define molecular characteristics of innate lymphoid cell classes and subsets.

The recognized diversity of innate lymphoid cells (ILCs) is rapidly expanding. Three ILC classes have emerged, ILC1, ILC2 and ILC3, with ILC1 and ILC3 including several subsets. The classification of some subsets is unclear, and it remains controversial whether natural killer (NK) cells and ILC1 cells are distinct cell types. To address these issues, we analyzed gene expression in ILCs and NK cells from mouse small intestine, spleen and liver, as part of the Immunological Genome Project. The results showed unique gene-expression patterns for some ILCs and overlapping patterns for ILC1 cells and NK cells, whereas other ILC subsets remained indistinguishable. We identified a transcriptional program shared by small intestine ILCs and a core ILC signature. We revealed and discuss transcripts that suggest previously unknown functions and developmental paths for ILCs.

Animals↗
PubMed2026

Integrated single-cell RNA sequencing and mendelian randomization analysis identifies causal immune-related driver genes in the heart failure inflammatory microenvironment.

BACKGROUND: Heart failure (HF) is a major global cause of cardiovascular death and disability. Chronic inflammation and immune dysregulation are critical in its development. The cardiac immune microenvironment, especially macrophages, drives HF progression, yet its molecular mechanisms and prognostic impact are not fully clear. This study aimed to identify causal immune-related driver genes in the HF inflammatory microenvironment. METHODS: We combined single-cell RNA sequencing (scRNA-seq) and Mendelian randomization (MR) to study how the inflammatory immune microenvironment affects HF risk. Using two public scRNA-seq datasets, we identified differentially expressed genes (DEGs) in HF heart tissues and selected 489 candidate genes. Causal relationships between these genes and HF were tested using expression quantitative trait loci (eQTL) data and HF genome-wide association study (GWAS) summary statistics. RESULTS: MR analysis showed that 65 genes were causally linked to HF risk. These genes were enriched in pathways related to cardiomyopathy, leukocyte migration, natural killer (NK) cell cytotoxicity, neutrophil extracellular traps, and NF-κB signaling. HF hearts displayed increased levels of macrophages, T cells, B cells, lymphoid cells, and mast cells, while neutrophils were reduced. CONCLUSIONS: Our integrated analysis reveals the central role of the cardiac inflammatory immune microenvironment in HF and identifies 65 key genes causally associated with HF susceptibility. These genes influence specific immune pathways and cell infiltration, shaping HF progression, and provide a basis for developing new biomarkers and immune-targeted therapies.

Heart failure (HF)↗
PubMed2026

Ascites reprograms innate lymphoid immune cells in ovarian cancer by promoting ILC2 enrichment and dysfunctional NK-cell states.

BACKGROUND: High-grade serous ovarian cancer (HGSOC) is commonly accompanied by malignant ascites, a clinically relevant tumor niche that promotes immune evasion, metastasis, and treatment resistance. Although natural killer (NK)-cell dysfunction has been described in ovarian cancer, the broader innate lymphoid landscape of ascites and the mechanisms linking ascites-derived signals to innate immune suppression remain insufficiently resolved. METHODS: We performed single-cell RNA sequencing of NK/innate lymphoid cells from ovarian cancer ascites to define cellular heterogeneity and differentiation states. Functional assays assessed NK-cell cytotoxicity, degranulation, and receptor expression following exposure to patient-derived ascites, with or without transforming growth factor-β (TGF-β) receptor inhibition. Proteomic profiling was used to characterize the soluble ascites milieu, and clinical associations were examined for innate lymphoid subsets. RESULTS: Single-cell analysis identified eight transcriptionally distinct NK/innate lymphoid states, including cytotoxic, precursor, early-like, tolerant/immunoregulatory, regulatory, proinflammatory, and innate lymphoid populations. Ovarian cancer ascites was characterized by depletion of cytotoxic and precursor NK-cell states together with enrichment of early-like, tolerant, regulatory, pro-inflammatory, and innate lymphoid cell (ILC) populations. Trajectory analysis indicated impaired maturation toward terminally differentiated cytotoxic NK cells. Notably, ascites contained an expanded population of programmed cell death protein 1 (PD-1)+ ILC2s, which were more abundant in patients with shorter progression-free survival. In functional assays, short-term exposure of healthy donor NK cells to ascites suppressed degranulation and tumor-cell killing, reduced expression of activating receptors including NKp30 and DNAM-1, increased inhibitory receptor expression, and shifted NK cells toward a CD56highCD16low phenotype. Proteomic profiling supported a soluble milieu consistent with type 2 immune skewing and NK-cell suppression. Importantly, TGF-β receptor inhibition partially restored NK-cell activation and function in the presence of ascites. CONCLUSIONS: HGSOC ascites establishes a type 2-skewed immunoregulatory niche that coordinately drives NK cell dysfunction and PD-1+ ILC2 accumulation. The findings identify TGF-β-linked suppression and ascites-associated immune regulators as candidate immunotherapeutic vulnerabilities for restoring antitumor immunity in ovarian cancer.

Humans↗
PubMed2026

Spatial niche remodeling of senescent liver-resident immune cells and its role in chronic liver diseases.

The liver serves the triple functions of metabolism, detoxification, and immune surveillance. Its unique immune microenvironment is shaped by continuous exposure to gut-derived antigens, pathogen-associated molecular patterns (PAMPs), and metabolites arriving via the portal vein, necessitating a delicate equilibrium between immune tolerance and effector activation. This equilibrium relies on the coordinated activities of diverse liver-resident immune cell populations-including Kupffer cells (KCs), liver sinusoidal endothelial cells (LSECs), hepatic stellate cells (HSCs), dendritic cells (DCs), tissue-resident memory T cells (TRM), innate-like T cells, including mucosal-associated invariant T (MAIT) cells, natural killer T (NKT) cells, and γδ T cells, innate lymphoid cells (ILCs, encompassing conventional NK cells and helper ILC subsets), and neutrophils. With advancing age and chronic injury, these resident immune cell populations undergo profound senescence-associated phenotypic reprogramming that is spatially organized along the portal-to-central axis of the hepatic lobule. Key mechanisms include: telomere dysfunction and DNA damage accumulation driving persistent activation of p53/p21 and p16/Rb pathways; mitochondrial dysfunction with mitochondrial DNA (mtDNA) leakage fueling the senescence-associated secretory phenotype (SASP) via the cyclic GMP-AMP synthase (cGAS)-stimulator of interferon genes (STING) pathway; epigenetic age acceleration, including genome-wide H3K27me3 heterochromatinization; and metabolic reprogramming toward glycolysis and lipid accumulation. This review proposes a "spatial niche remodeling" framework to integrate these cell-intrinsic senescence programs with their lobular context, intercellular communication network rewiring, and pathogenic roles across the spectrum of chronic liver disease-from steatosis through steatohepatitis, fibrosis, cirrhosis, to hepatocellular carcinoma. We critically evaluate emerging senotherapeutic strategies targeting specific liver-resident immune cell subsets, discuss the barriers to clinical translation, and identify priority areas for future investigation, including the application of spatial multi-omics, humanized models, and epigenetic clock-guided clinical trials.

Kupffer cells↗
PubMed2025

Immune microenvironment in hepatocellular carcinoma: from pathogenesis to immunotherapy.

Hepatocellular carcinoma (HCC) is an increasingly prevalent and deadly disease that is initiated by different etiological factors, such as alcohol-associated liver disease (ALD), metabolic dysfunction-associated steatohepatitis (MASH), viral hepatitis, and other hepatotoxic and hepatocarcinogenic agents. The tumor microenvironment (TME) of HCC is characterized by several different fibroblastic and immune cell types, all of which affect the initiation, progression and metastasis of this malignant cancer. This complex immune TME can be divided into an innate component that includes macrophages, neutrophils, dendritic cells, myeloid-derived suppressor cells, mucosal-associated invariant T cells, natural killer cells, natural killer T cells, and innate lymphoid cells, as well as an adaptive component that includes CD4+ T cells, CD8+ T cells, regulatory T cells, and B cells. In this review, we discuss the latest findings shedding light on the direct or indirect roles of these immune cells (and fibroblastic-like cells such as hepatic stellate cells) in the pathogenesis of HCC. Henceforth, further characterization of this heterogeneous TME is highly important for studying the progression of HCC and developing novel immunotherapeutic treatment options. In line with this, we also review novel groundbreaking experimental techniques and animal models aimed at specifically elucidating this complex TME and discuss emerging immune-based therapeutic strategies intended to treat HCC and predict the efficacy of these immunotherapies.

Humans↗
PubMed2026

Multi-omics identifies lipid accumulation in Myalgic Encephalomyelitis/Chronic Fatigue Syndrome cell lines: a case-control study.

BACKGROUND: In recent years, evidence has indicated a metabolic shift towards increased demand for lipids in various lymphoid cell populations from people with Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS). We previously screened the mitochondrial function and gene expression of B cell-derived lymphoblastoid cell lines (LCLs) generated from the blood of people with ME/CFS to characterise a model for hypothesis discovery and testing, observing elevated expression of gene products facilitating amino acid and fatty acid degradation for energy. METHOD: In this follow-up study we have expanded this characterisation by profiling the polar metabolomes and non-polar lipidomes of an all-female cohort of 17 healthy control and 15 ME/CFS LCLs, and we integrated this new data with the previously generated proteomic and transcriptomic data. RESULTS: In the polar metabolome we detected no significantly altered individual features, while integrated multi-omic analysis by MetaboAnalyst indicated 15 dysregulated pathways. Next, in the non-polar lipidome, we identified that PC(O-38:4) had significantly reduced levels in ME/CFS LCLs and was almost entirely discriminative of ME/CFS status. Among all detected classes of lipids we found that triradylglycerolipids ("triglycerides"), diradylglycerolipids and fatty acids were the most significantly affected and were elevated, and that most lipids exhibited average levels higher than in healthy controls. BioPAN pathway analysis of the lipidomic data predicted a more-active gene product that we confirmed to be significantly elevated in both our proteomic and transcriptomic data, this being phosphatidylserine synthase 1 (PTDSS1), plus 7 other gene products that were concordantly altered in expression in the transcriptomic data. We also found that ME/CFS LCLs exhibited a significant tendency towards more saturated lipid content. CONCLUSIONS: LCLs generated from circulating B cells from people with ME/CFS show accumulation of lipids, skewed lipid profiles and altered activity of related metabolic enzymes such as PTDSS1. These findings will inform future hypothesis-driven studies of primary lymphoid cell populations from people with ME/CFS to dissect specific immunometabolic mechanisms that may be involved in the syndrome, particularly relating to intersections between lipid abnormalities and potential effects on immune cell effector functions.

Fatigue Syndrome, Chronic↗
PubMed2026

Digital and computational morphology in hematology: current platforms, clinical evidence, and future requirements.

INTRODUCTION: Morphologic examination of peripheral blood and bone marrow remains central to the diagnosis and classification of hematologic disorders. Conventional optical microscopy, however, is labor-intensive, dependent on operator expertise, and affected by interobserver variability. Digital morphology has developed from automated image acquisition and cell pre-classification into a broader field that includes whole-slide imaging, remote review, quantitative morphometry, and artificial intelligence-based analysis. CONTENT: This review examines current applications of digital morphology in peripheral blood, bone marrow aspirates, malaria detection, and body-fluid analysis. Commercial platforms are evaluated with particular attention to the distinction between raw automated pre-classification, expert digital post-classification, and comparison with independent optical microscopy. Digital systems generally perform well for common mature leukocyte populations but remain less reliable for rare or diagnostically critical cells, including blasts, abnormal lymphoid cells, plasma cells, and intermediate maturation stages. Research systems increasingly extend analysis from individual-cell classification to whole-slide, specimen-level, and patient-level assessment. SUMMARY: Digital morphology can improve standardization, image traceability, remote consultation, education, proficiency testing, quality assurance, and selected aspects of laboratory workflow. Its clinical value depends on appropriate validation, transparent reporting of reference methods, recognition of algorithm-specific failure modes, and clearly defined criteria for expert review and conventional microscopy. Human expertise remains essential not only for validating results but also for adapting cell taxonomies and interpretive rules to evolving classifications of hematologic diseases. OUTLOOK: Future progress will require representative multicenter datasets, harmonized morphologic terminology, external validation, interoperability with laboratory information systems, and continuous monitoring after software or hardware updates. Integration of morphology with quantitative hematology, flow cytometry, cytogenetics, genomics, and clinical data may support more comprehensive computational diagnosis. Digital platforms may also broaden access to specialist expertise, training, and quality programs in resource-limited institutions and regions, provided that infrastructure, governance, and professional competency are adequately supported.

artificial intelligence↗
PubMed2025

DNA-binding affinity and specificity determine the phenotypic diversity in BCL11B-related disorders.

BCL11B is a Cys2-His2 zinc-finger (C2H2-ZnF) domain-containing, DNA-binding, transcription factor with established roles in the development of various organs and tissues, primarily the immune and nervous systems. BCL11B germline variants have been associated with a variety of developmental syndromes. However, genotype-phenotype correlations along with pathophysiologic mechanisms of selected variants mostly remain elusive. To dissect these, we performed genotype-phenotype correlations of 92 affected individuals harboring a pathogenic or likely pathogenic BCL11B variant, followed by immune phenotyping, analysis of chromatin immunoprecipitation DNA-sequencing data, dual-luciferase reporter assays, and molecular modeling. These integrative analyses enabled us to define three clinical subtypes of BCL11B-related disorders. It is likely that gene-disruptive BCL11B variants and missense variants affecting zinc-binding cysteine and histidine residues cause mild to moderate neurodevelopmental delay with increased propensity for behavioral and dental anomalies, allergies and asthma, and reduced type 2 innate lymphoid cells. Missense variants within C2H2-ZnF DNA-contacting α helices cause highly variable clinical presentations ranging from multisystem anomalies with demise in the first years of life to late-onset, hyperkinetic movement disorder with poor fine motor skills. Those not in direct DNA contact cause a milder phenotype through reduced, target-specific transcriptional activity. However, missense variants affecting C2H2-ZnFs, DNA binding, and "specificity residues" impair BCL11B transcriptional activity in a target-specific, dominant-negative manner along with aberrant regulation of alternative DNA targets, resulting in more severe and unpredictable clinical outcomes. Taken together, we suggest that the phenotypic severity and variability is largely dependent on the DNA-binding affinity and specificity of altered BCL11B proteins.

Adolescent↗
PubMed2023

Intratumor childhood vaccine-specific CD4+ T-cell recall coordinates antitumor CD8+ T cells and eosinophils.

BACKGROUND: Antitumor mechanisms of CD4+ T cells remain crudely defined, and means to effectively harness CD4+ T-cell help for cancer immunotherapy are lacking. Pre-existing memory CD4+ T cells hold potential to be leveraged for this purpose. Moreover, the role of pre-existing immunity in virotherapy, particularly recombinant poliovirus immunotherapy where childhood polio vaccine specific immunity is ubiquitous, remains unclear. Here we tested the hypothesis that childhood vaccine-specific memory T cells mediate antitumor immunotherapy and contribute to the antitumor efficacy of polio virotherapy. METHODS: The impact of polio immunization on polio virotherapy, and the antitumor effects of polio and tetanus recall were tested in syngeneic murine melanoma and breast cancer models. CD8+ T-cell and B-cell knockout, CD4+ T-cell depletion, CD4+ T-cell adoptive transfer, CD40L blockade, assessments of antitumor T-cell immunity, and eosinophil depletion defined antitumor mechanisms of recall antigens. Pan-cancer transcriptome data sets and polio virotherapy clinical trial correlates were used to assess the relevance of these findings in humans. RESULTS: Prior vaccination against poliovirus substantially bolstered the antitumor efficacy of polio virotherapy in mice, and intratumor recall of poliovirus or tetanus immunity delayed tumor growth. Intratumor recall antigens augmented antitumor T-cell function, caused marked tumor infiltration of type 2 innate lymphoid cells and eosinophils, and decreased proportions of regulatory T cells (Tregs). Antitumor effects of recall antigens were mediated by CD4+ T cells, limited by B cells, independent of CD40L, and dependent on eosinophils and CD8+ T cells. An inverse relationship between eosinophil and Treg signatures was observed across The Cancer Genome Atlas (TCGA) cancer types, and eosinophil depletion prevented Treg reductions after polio recall. Pretreatment polio neutralizing antibody titers were higher in patients living longer, and eosinophil levels increased in the majority of patients, after polio virotherapy. CONCLUSION: Pre-existing anti-polio immunity contributes to the antitumor efficacy of polio virotherapy. This work defines cancer immunotherapy potential of childhood vaccines, reveals their utility to engage CD4+ T-cell help for antitumor CD8+ T cells, and implicates eosinophils as antitumor effectors of CD4+ T cells.

Mice↗
PubMed2025

Cellular imbalance in proximal and distal lung of CFTR-/- sheep in utero and at birth.

BACKGROUND: The Lung is the major focus of therapeutic approaches for the inherited disorder cystic fibrosis (CF) as without treatment lung disease is life-limiting. However, the initiating events that predispose the CF lung to cycles of infection, inflammation and resultant tissue damage are still unclear. Inflammation may occur in the CF lung prior to birth in human and several large animal models suggesting an in utero origin for the disease and encouraging further studies prior to birth. METHODS: Here we used the sheep model of CF (CFTR-/-) and age-matched wild-type (WT) sheep of the same breed to investigate the single cell transcriptomes of proximal and distal lung tissue at 80 days and 120 days of gestation and at term (147 days). Single cell RNA-seq was performed on tissues from 4 to 7 animals of each genotype (WT and CFTR-/-) at each time point. RESULTS: At term, FOXJ1-expressing ciliated cells are overrepresented in both lung regions from CFTR-/- lambs, while secretory epithelial and basal cells are underrepresented in proximal lung, as are T cells and monocytes in distal lung. The imbalance in ciliated and basal cells was confirmed by immunohistochemistry. At 120 days of gestation, lymphoid cells are slightly more abundant in proximal and distal lung from CFTR-/- animals compared to WT, consistent with the transient CF-associated inflammatory response in utero. At 80 days of gestation, T and B cells are underrepresented in both lung regions. CONCLUSIONS: The differences in epithelial cell abundance observed in the CFTR-/- lambs at term may reflect sequelae from the loss of CFTR on lung development and differentiation in utero. These findings provide novel insights into the cellular mechanisms of pathology and may be relevant to the design of new therapeutic approaches for CF lung disease.

Animals↗
PubMed2025

USP7 Inhibitors Destabilize EBNA1 and Suppress Epstein-Barr Virus Tumorigenesis.

Epstein-Barr virus (EBV) is a ubiquitous human ɣ-herpesvirus implicated in various malignancies, including Burkitt's lymphoma and gastric carcinomas. In most EBV-associated cancers, the viral genome is maintained as an extrachromosomal episome by the EBV nuclear antigen-1 (EBNA1). EBNA1 is considered to be a highly stable protein that interacts with the ubiquitin-specific protease 7 (USP7). Here, we show that pharmacological inhibitors and small interfering RNA (siRNA) targeting USP7 reduce EBNA1 protein levels in a proteosome-dependent manner. Proteomic analysis revealed that USP7 inhibitor GNE6776 altered the EBNA1 protein interactome, including disrupting USP7 association with EBNA1. GNE6776 also inhibited EBNA1 binding to EBV oriP DNA and reduced viral episome copy number. Transcriptomic studies revealed that USP7 inhibition affected chromosome segregation and mitotic cell division pathways in EBV+ cells. Finally, we show that GNE6776 selectively inhibited EBV+ gastric and lymphoid cell proliferation in cell culture and slowed EBV+ tumor growth in mouse xenograft models. These findings suggest that USP7 inhibitors perturb EBNA1 stability and function and may be exploited to treat EBV latent infection and tumorigenesis.

Ubiquitin-Specific Peptidase 7↗
PubMed2024

Tuft cell acetylcholine is released into the gut lumen to promote anti-helminth immunity.

Upon parasitic helminth infection, activated intestinal tuft cells secrete interleukin-25 (IL-25), which initiates a type 2 immune response during which lamina propria type 2 innate lymphoid cells (ILC2s) produce IL-13. This causes epithelial remodeling, including tuft cell hyperplasia, the function of which is unknown. We identified a cholinergic effector function of tuft cells, which are the only epithelial cells that expressed choline acetyltransferase (ChAT). During parasite infection, mice with epithelial-specific deletion of ChAT had increased worm burden, fitness, and fecal egg counts, even though type 2 immune responses were comparable. Mechanistically, IL-13-amplified tuft cells release acetylcholine (ACh) into the gut lumen. Finally, we demonstrated a direct effect of ACh on worms, which reduced their fecundity via helminth-expressed muscarinic ACh receptors. Thus, tuft cells are sentinels in naive mice, and their amplification upon helminth infection provides an additional type 2 immune response effector function.

Animals↗
PubMed2026

Endothelial MHC expression is required to initiate T cell-mediated rejection of 3D-printed skin grafts.

Vascularized skins were 3D printed using single donor human fibroblasts, pericytes, keratinocytes, and endothelial cells (ECs), the latter either unmodified (WT-ECs) or deleted of MHC molecules (KO-ECs). Adult MISTRG6 immunodeficient mice neonatally inoculated with adult human hematopoietic stem cells (HSCs) received printed skin allogeneic to the HSCs and were boosted 3 weeks after grafting with human PBMCs autologous to the HSCs. HSC inoculation alone produced low levels of circulating human myeloid and lymphoid cells without affecting grafts; PBMC boosting dramatically increased circulating human CD4+ T cells and boosted CD8+ T cells only in mice with WT-EC grafts. These grafts became infiltrated by human macrophages, dendritic cells, CD4+ and CD8+ T cells and showed evidence of rejection. Shared T cell clones were present in skin and spleen. KO-EC grafts had minimal infiltration of graft or spleen without rejection, despite MHC molecule expression on other graft cell types.

Animals↗
PubMed2026

Somatic Mitochondrial-Nuclear DNA Transfer in Lymphoproliferative Disorders.

INTRODUCTION: Somatic mitochondrial-nuclear DNA transfer (SMNT) is a process by which mitochondrial DNA (mtDNA), of varying sizes, integrate into the nuclear genome and has been previously reported in solid tumours. METHODS: EuroClonality-NGS DNA Capture sequencing data from 755 lymphoid malignancies and 59 lymphoid cell lines were analysed for SMNT-associated structural variants. RESULTS: Five malignancies (0.66%) harboured SMNTs, predominantly involving IGH genes, with one PTEN gene disruption identified. Breakpoint features supported non-homologous end joining-mediated integration. CONCLUSION: SMNTs are rare but recurrent events in lymphoid malignancies and may represent stable clonal markers for minimal residual disease monitoring. TRIAL REGISTRATION: The authors have confirmed clinical trial registration is not needed for this submission.

Journal Article↗
PubMed2026

Testicular aggressive B-cell lymphoma with plasmablastic morphology harboring concurrent IGH::MYC and IGH::BCL2 rearrangements.

BACKGROUND: Aggressive B-cell lymphomas with plasmablastic morphology are uncommon neoplasms that may exhibit overlapping morphologic, immunophenotypic, and genetic features of plasmablastic lymphoma (PBL) and double-hit lymphoma (DHL). Concurrent IGH::MYC and IGH::BCL2 rearrangements are rarely encountered in this setting, particularly in the testis. Here, we describe an unusual case presenting significant diagnostic challenges at the interface between PBL and DHL. CASE PRESENTATION: We report a 66-year-old, immunocompetent man presenting with a 5 cm left testicular mass. Histologic examination revealed diffuse proliferation of large atypical lymphoid cells with plasmablastic morphology. Immunohistochemically, the tumor expressed CD138, CD38, and MUM1, with focal BCL2, c-MYC protein, and CD79a positivity, while CD20, CD19, PAX5, CD10, BCL6, and ALK were negative. EBV-encoded RNA in situ hybridization was negative. Fluorescence in situ hybridization identified IGH::MYC [t(8;14)] rearrangement in 45% and IGH::BCL2 [t(14;18)] rearrangement in 21% of analyzed nuclei. Next-generation sequencing additionally revealed BRAF V600E mutation, CDKN2A deletion, and human leukocyte antigen class I genomic alterations. CONCLUSION: This case highlights a rare testicular aggressive B-cell lymphoma with plasmablastic morphology and concurrent IGH::MYC and IGH::BCL2 rearrangements, representing a diagnostically challenging neoplasm at the interface between PBL and DHL. Our findings underscore the value of integrated morphologic, immunophenotypic, cytogenetic, and molecular analyses in evaluating aggressive B-cell lymphomas with plasmablastic features arising in immune-privileged sites.

Humans↗