Journal of Leukocyte Biology

Glycosylated RNA molecules (glycoRNAs) that can be bound by lectins have been demonstrated on the surfaces of leukocytes, but their physiologic function(s) was not known. A recent paper (PMID 38262409) demonstrates that at least one function is to promote capture and rolling of neutrophils in the vasculature. Of interest, the neutrophil glycoRNAs bind to P-selectin, but not E-selectin.

Eosinophil sombrero vesicles (EoSVs) are large tubular carriers resident in the cytoplasm of human eosinophils, identifiable by transmission electron microscopy (TEM), and important for immune mediator transport. Increased EoSV formation occurs in activated eosinophils in vitro and in vivo. In tissue sites of eosinophilic cytolytic inflammation, extracellular EoSVs are noted, but their frequency and significance in eosinophil-associated diseases (EADs) remain unclear. Here, we performed comprehensive quantitative TEM analyses and electron tomography to investigate the numbers, density, integrity, and three-dimensional (3D) structure of EoSVs in different biopsy tissues from five prototypic EADs (eosinophilic chronic rhinosinusitis/nasal sinuses, ulcerative colitis/intestines, hypereosinophilic syndrome/skin, dermatitis/skin, and schistosomiasis/rectum)...

Classic myeloproliferative neoplasms lacking the Philadelphia chromosome are stem cell disorders characterized by the proliferation of myeloid cells in the bone marrow and increased counts of peripheral blood cells. The occurrence of thrombotic events is a common complication in myeloproliferative neoplasms. The heightened levels of cytokines play a substantial role in the morbidity and mortality of these patients, establishing a persistent proinflammatory condition that culminates in thrombosis. The etiology of thrombosis remains intricate and multifaceted, involving blood cells and endothelial dysfunction, the inflammatory state, and the coagulation cascade, leading to hypercoagulability...

Macrophage and osteoclast proliferation, differentiation and survival are regulated by colony-stimulating factor-1 receptor (CSF1R) signaling. Osteopetrosis associated with Csf1 and Csf1r mutations has been attributed to the loss of osteoclasts and deficiency in bone resorption. Here we demonstrate that homozygous Csf1r mutation in rat leads to delayed postnatal skeletal ossification associated with substantial loss of osteal macrophages (osteomacs) in addition to osteoclasts. Osteosclerosis and site-specific skeletal abnormalities were reversed by intraperitoneal transfer of wild-type bone marrow cells (BMT) at weaning...

No abstract text is available yet for this article.

Influenza virus infection is a worldwide challenge that causes heavy burdens on public health. The mortality rate of severe influenza patients is often associated with hyperactive immunological abnormalities characterized by hypercytokinemia. Due to the continuous mutations and the occurrence of drug-resistant influenza virus strains, the development of host-directed immunoregulatory drugs is urgently required. Platycodon grandiflorum is among the top 10 herbs of traditional Chinese medicine used to treat pulmonary diseases...

Interleukin (IL)-33 is a key driver of T helper 2 (Th2) cell polarization. Endoplasmic reticulum (ER) stress plays a role in the skewed T cell activation. The objective of this project is to elucidate the role of IL-33 derived from macrophages in inducing Th2 polarization in the airways. In this study, bronchoalveolar lavage fluids (BALF) were collected from patients with asthma and healthy control subjects. Macrophages were isolated from the BALF by flow cytometry cell sorting. An asthmatic mouse model was established using the ovalbumin/alum protocol...

Macropinocytosis is a large-scale endocytosis process that is primarily observed in phagocytes as part of their cellular function to ingest antigens. Once phagocytes encounter gram-negative bacteria, the receptor proteins identify lipopolysaccharides (LPSs), which trigger radical membrane ruffles that gradually change to cup-like structures. The open area of the cups closes to generate vesicles called macropinosomes. The target bacteria are isolated by the cups and engulfed by the cells as the cups close. In addition to its ingestion function, macropinocytosis also regulates the AKT pathway in macrophages...

Implants and medical devices are efficient and practical therapeutic solutions for a multitude of pathologies. Titanium and titanium alloys are used in orthopedics, dentistry, and cardiology. Despite very good mechanical properties, and corrosion resistance titanium implants can fail due to inflammatory or tissue-degradation related complications. Macrophages are major immune cells that control acceptance of failure of the implant. In this study, for the first time, we have performed a systematic analysis of the response of differentially activated human macrophages (M(Control), M(IFNγ) and M(IL-4)) to the polished and porous titanium surfaces in order to identify the detrimental effect of titanium leading to the tissue destruction and chronic inflammation...

Eosinophilic esophagitis is a chronic inflammatory disorder of the esophagus. Over the past 25 yr, great strides have been made toward understanding its pathogenesis, in part due to studies in several types of animal models. The vast majority of these models have been characterized in mice. In this review, we summarize the histopathological features of eosinophilic esophagitis recapitulated by these animal models, as well as discuss their strengths and weaknesses.

The tumor microenvironment provides a unique opportunity to gain insight into the relationship and crosstalk between different cell types. In this context, little is known about the interaction between γδ T cells and neutrophils, which are innate immune cells abundant in the tumor microenvironment. Interestingly, both γδ T cells and neutrophils are heterogenous, may play diverse regulatory roles and have been shown to have both pro-tumor and anti-tumor functions. In this editorial, we discuss recent advances in the understanding of interplay between γδ T cells and neutrophils in cancer and provide insights and future directions highlighting the role these interactions may play in cancer...

Fungal infections present a significant global public health concern, impacting over one billion individuals worldwide and resulting in more than 3 million deaths annually. Despite considerable progress in recent years, the management of fungal infections remains challenging. The limited development of novel diagnostic and therapeutic approaches is largely attributed to our incomplete understanding of the pathogenetic mechanisms involved in these diseases. Recent research has highlighted the pivotal role of cellular metabolism in regulating the interaction between fungi and their hosts...

No abstract text is available yet for this article.

IL-21/IL-21R signaling dysregulation is linked to multiple chronic intestinal inflammatory disorders in humans and animal models of human diseases. In addition to its critical requirement for the generation and development of germinal center B cells, IL-21/IL-21R signaling can also regulate the effector functions of a variety of T cell subsets. The antibody-mediated abrogation of IL-21/IL-21R signaling led to the impaired expression of IFN-γ by mucosal CD4+ T cells from human subjects with colitis, suggesting an IL-21/IL-21R-triggered positive feedback loop of the TH1 immune response in the colon...

Tuberculosis caused by the pathogen Mycobacterium tuberculosis leads to increased mortality and morbidity worldwide. The prevalence of highly drug resistant strains has reinforced the need for greater understanding of host-pathogen interactions at the cellular and molecular levels. Our previous work demonstrated critical roles of calcium ion channels in regulating protective responses to mycobacteria. In this report we deciphered the roles of inwardly rectifying K+ ion channel Kir2.1 in epithelial cells. Data showed that infection of epithelial cells (and macrophages) increases the surface expression of Kir2...

Toll-like receptors are pattern recognition receptors that bridge the innate and adaptive immune responses and are critical for host defense. Most studies of Toll-like receptors have focused upon their roles in myeloid cells. B lymphocytes express most Toll-like receptors and are responsive to Toll-like receptor ligands, yet Toll-like receptor-mediated signaling in B cells is relatively understudied. This is an important knowledge gap, as Toll-like receptor functions can be cell type specific. In striking contrast to myeloid cells, TRAF3 inhibits TLR-mediated functions in B cells...

Pancreatic ductal adenocarcinoma (PDAC) is characterized by poor response to all therapeutic modalities and dismal prognosis. The presence of tertiary lymphoid structures (TLSs) in various solid cancers is of crucial prognostic significance, highlighting the intricate interplay between the tumor microenvironment and immune cells aggregation. However, the extent to which TLS and immune status affect PDAC prognosis remains incompletely understood. Here, we sought to unveil the unique properties of TLS in PDAC by leveraging both single-cell and bulk transcriptomics, and culminating in a risk model that predicts clinical outcomes...

B-1a cells, a regulatory subset of B lymphocytes, produce natural IgM and IL-10. Neutrophil extracellular traps (NETs) play a crucial role in pathogen defense, but their excessive formation during sepsis can cause further inflammation and tissue damage. In sepsis, extracellular cold-inducible RNA-binding protein (eCIRP), a damage-associated molecular pattern, is released to induce NET formation. We hypothesize that B-1a cells clear NETs to prevent sepsis-induced injury. Sepsis in mice was induced by injecting 1 × 107 and 5 × 107 CFU E...

In chronic inflammation regulatory immune cells, such as regulatory T cells and myeloid-derived suppressor cells (MDCS) can develop. Local signals in the inflamed tissue, such as cytokines and eicosanoids, but also contact dependent signals, can promote MDSC development. In the liver, hepatic stellate cells (HSC) may provide such signals via the expression of CD44. MDSC generated in the presence of HSC and anti-CD44 antibodies were functionally and phenotypically analyzed. We found that both monocytic (M-) and polymorphonuclear (PMN-) MDSC generated in the presence of αCD44 antibodies were less suppressive towards T cells as measured by T cell proliferation and cytokine production...

Triple-negative breast cancer (TNBC) is a high-risk form of breast cancer with a high metastatic potential and lack of effective therapies. Immunotherapy has shown encouraging clinical benefits, and its efficacy in TNBC is affected by immunocyte infiltration in the tumor microenvironment (TME). Phosphoglycerate mutase 1 (PGAM1) is a key enzyme involved in cancer metabolism; however, its role in the TME remains unclear. In this study, we aimed to investigate the role of PGAM1 in TNBC and determine the potential of PGAM1 inhibition in combination with anti-PD-1 immunotherapy...