Journal of Leukocyte Biology

Intestinal eosinophils express the aryl hydrocarbon receptor (AHR), an environmental sensor and ligand-activated transcription factor that responds to dietary or environmental ligands. AHR regulates tissue adaptation, survival, adhesion, and immune functions in intestinal eosinophils. The AHR repressor (AHRR) is itself induced by AHR and believed to limit AHR activity in a negative feedback loop. We analysed gene expression in intestinal eosinophils from WT and AHRR-KO mice and found that AHRR did not suppress most AHR-dependent genes...

Eosinophils, recognized for their immune and remodeling functions and participation in allergic inflammation, have recently garnered attention due to their impact on host metabolism, especially in the regulation of adipose tissue. Eosinophils are now known for their role in adipocyte beiging, adipokine secretion, and adipose tissue inflammation. This intricate interaction involves complex immune and metabolic processes, carrying significant implications for systemic metabolic health. Importantly, the interplay between eosinophils and adipocytes is bidirectional, revealing the dynamic nature of the immune-metabolic axis in adipose tissue...

Precise synapse elimination is essential for the establishment of a fully developed neural circuit during brain development and higher function in adult brain. Beyond immune and nutrition support, recent groundbreaking studies have revealed that phagocytic microglia and astrocytes can actively and selectively eliminate synapses in normal and diseased brains, thereby mediating synapse loss and maintaining circuit homeostasis. Multiple lines of evidence indicate that the mechanisms of synapse elimination by phagocytic glia are not universal but rather depend on specific contexts and detailed neuron-glia interactions...

The noncanonical NF-κB pathway is involved in lymphoid organ development, B cell maturation, and cytokine production. However, new research has demonstrated that this pathway is also key for the orderly and sequential maturation of myeloid cells, including neutrophils and eosinophils. When this pathway is disrupted or constitutively activated, aberrations in hematopoietic stem and progenitor cell (HSPC) survival and proliferation, as well as subsequent granulopoiesis and eosinophilopoiesis are affected...

It has been found that CD226 plays an important role in regulating macrophage function, but its expression and function in macrophages during renal fibrogenesis have not been studied. Our data demonstrated that CD226 expression in macrophages was obviously upregulated in the unilateral ureteral obstruction model, while CD226 deficiency attenuated collagen deposition in renal interstitium along with fewer M1 within renal cortex and renal medulla and a lower level of proinflammatory factors compared to that of control littermates...

N6-methyladenosine (m6A) is a RNA modification that can regulate post-transcriptional processes including RNA stability, translation, splicing and nuclear export. In CD4+ lymphocytes, m6A modifications have been demonstrated to play a role in early differentiation processes. The role of m6A in CD4+ T cell activation and effector function remains incompletely understood. To assess the role of m6A in CD4+ T lymphocyte activation and function, we assessed the transcriptome-wide m6A landscape of human primary CD4+ T cells by methylated RNA immunoprecipitation (meRIP) sequencing...

Primary Biliary Cholangitis (PBC) and Autoimmune Hepatitis (AIH) are autoimmune diseases that target hepatocytes and bile duct cells, respectively. Despite their shared autoimmune nature, the differences in immunologic characteristics between them remain largely unexplored. This study seeks to elucidate the unique immunological profiles of PBC and AIH, and to identify key differences. We comprehensively analyzed various T-cell subsets and their receptor expression in a cohort of 45 patients, including 27 PBC and 18 AIH cases...

The Mammalian Target of Rapamycin (mTOR) pathway plays a key role in determining immune cells function through modulation of their metabolic status. By specific deletion of Rictor in CD11c+ myeloid cells (referred to here as CD11cRicΔ/Δ), this study investigated the role of mTOR complex 2 (mTORC2) signalling in dendritic cells (DCs) function in mice. We showed that upon DSS-induced colitis, lack of mTORC2 signalling CD11c+ cells diminishes colitis score, and abrogates dendritic cell (DC) migration to the mesenteric lymph nodes (MLN), thereby diminishing the infiltration of T helper (Th) 17 cells in the lamina propria (LP) and subsequent inflammation...

Link et al. conducted a controlled study comparing the impacts of ketogenic and vegan diets on energy intake and immune function in humans. Deep -omics analyses revealed distinct effects of each diet on the immune system, including changes in cell populations and blood transcriptomes indicative of diet-induced shifts between adaptive and innate immunity. The study highlights the potentially significant, rapid impact of diet on immune function and health.

Sorting nexin (SNX) 27 is a unique member of the SNX family of proteins that mediates the endosome-to-plasma membrane trafficking of cargos bearing a PSD95/Dlg1/ZO-1 (PDZ)-binding motif. In brain, SNX27 regulates synaptic plasticity, and its dysregulation contributes to cognitive impairment and neuronal degeneration. In T lymphocytes, SNX27 partners with diacylglycerol (DAG) kinase ζ (DGKζ) to facilitate polarized traffic and signaling at the immune synapse (IS). By silencing SNX27 expression in a human T cell line, we demonstrate that SNX27 is a key regulator of the early T cell tyrosine-based signaling cascade...

Transarterial embolization (TACE), the first-line treatment for hepatocellular carcinoma (HCC), does not always lead to promising outcomes in all patients. A better understanding of how the immune lymphocytes changes after TACE might be the key to improve the efficacy of TACE. However, there are few studies evaluating immune lymphocytes in TACE patients. Therefore, we aimed to evaluate the short- and long-term effects of TACE on lymphocyte subsets in patients with HCC to identify those that predict TACE prognosis...

Calcineurin - nuclear factor of activated T-cell (CN-NFAT) inhibitors are widely clinically used drugs for immunosuppression but besides their required T-cell response inhibition, they also undesirably affect innate immune cells. Disruption of innate immune cell function can explain the observed susceptibility of CN-NFAT inhibitors-treated patients to opportunistic fungal infections. Neutrophils play an essential role in innate immunity as a defense against pathogens, however, the effect of CN-NFAT inhibitors on neutrophil function was poorly described...

In adults, monocytes and neutrophils play important roles in the hyper-inflammatory responses' characteristic of severe forms of SARS-CoV-2 infection. We assessed leukocyte activation in 55 children attending the emergency department for acute fever between March 2020 and September 2021. The following markers were analyzed by flow cytometry: CD169 and HLA-DR on monocytes, CD64 and CD16 on neutrophils, CD38 on lymphocytes TCD8. Fifteen of the children had SARS-CoV-2 infection, 15 had bacterial infections, 15 had inflammatory diseases...

Regulatory T cells (Tregs) play a crucial role in the homeostasis of the immune response. Tregs are mainly generated in the thymus and are characterized by the expression of Foxp3, which is considered the Treg master transcription factor. In addition, Tregs can be induced from naïve CD4+ T cells to express Foxp3 under specific conditions both in vivo (pTregs) and in vitro (iTregs). Both subsets tTregs and pTregs are necessary for the establishment of immune tolerance to self and non-self antigens. Although it has been postulated that iTregs may be less stable compared to tTregs, mainly due to epigenetic differences, accumulating evidence in animal models shows that iTregs are stable in vivo and could be used for the treatment of inflammatory disorders including autoimmune diseases and allogeneic transplant rejection...

The treatment of non-healing wounds, such as diabetic ulcers, remains a critical clinical challenge. Recent breakthroughs in cell therapy have shown great promise, with one primary focus on preparing cells with comprehensive reparative functions and foreseeable safety. In our previous study, we recapitulated the pro-regenerative and immunosuppressive functions of tumor-associated macrophages (TAMs) in non-tumor-derived macrophages, endowing the latter with characteristics for promoting diabetic wound healing - termed TAMs-educated macrophages (TAMEMs)...

Intercellular cell adhesion molecule 1 (ICAM-1) is a cell surface glycoprotein with a vital role in the immune response to pathogens. The expression pattern of ICAM-1 is wide-ranging, encompassing endothelial cells, epithelial cells and neutrophils. Recent work has characterized the role of ICAM-1 in murine neutrophils, but the function of human neutrophil ICAM-1 is incompletely understood. Herein, we investigated the expression and role of ICAMs in human neutrophils in vitro and in vivo. Our findings show clear expression of ICAM-1, -3 and -4 on peripheral blood-derived neutrophils and demonstrate that the pathogen-associated molecular pattern (PAMP) lipoteichoic acid (LTA) is an inducer of ICAM-1 expression in vitro...

This issue highlights and details the programme and scientific presentations at the International Eosinophil Society's 12th biennial Symposium, which was held in Hamilton, Ontario, Canada in July 2023. The meeting included sessions on regulation of eosinophil development; cell death, stress, and autophagy in eosinophils; local immunity interactions of eosinophils with multiple cell types; eosinophils in host defense; eosinophils and mast cells in gastrointestinal disorders; reciprocal interactions between eosinophils and the microbiome in homeostasis and dysbiosis; and, eosinophils in tissue injury and repair, in tumor biology and cancer therapy...

Conventional treatments have shown a limited efficacy for pancreatic cancer, and immunotherapy is an emerging option for treatment of this highly fatal malignancy. Neoantigen is critical to improving the efficacy of tumor-specific immunotherapy. The cancer and peripheral blood specimens from human leukocyte antigen (HLA)-A0201 positive pancreatic cancer patient were subjected to next-generation sequencing and bioinformatics analyses were performed to screen high-affinity and highly stable neoepitopes. The activation of cytotoxic T lymphocytes (CTLs) by the mutBCL2A111-20 neoepitope targeting B-cell lymphoma 2-related protein A1 (BCL2A1) mutant epitope was investigated, and the cytotoxicity of mutBCL2A111-20 neoepitope-specific CTLs to pancreatic cancer cells was evaluated...

Total glucoside of paeonia (TGP) and its main active ingredient paeoniflorin, extracted from the Chinese herb Paeonia Lactiflora Pallas, exhibit potent immunomodulatory effects. TGP has been shown to inhibit inflammatory responses and disease progression in experimental models of multiple autoimmune diseases (AIDs), including rheumatoid arthritis, systemic lupus erythematosus, Sjogren's syndrome, psoriasis, etc. TGP shows broad immunomodulatory effects on many immune cells such as T cells, macrophages, and dendritic cells, by regulating their activation, proliferation, differentiation, and production of effector molecules...

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