Journal of Leukocyte Biology

CD115, the receptor for colony stimulating factor 1 (CSF-1), is essential for survival and differentiation of monocytes and macrophages and is therefore frequently used to define monocyte subsets and their progenitors in immunological assays. However, CD115 surface expression and detection by flow cytometry is greatly influenced by cell isolation and processing methods, organ source and disease context. In a systematic analysis of murine monocytes we define experimental conditions that preserve or limit CD115 surface expression and staining by flow cytometry...

Sepsis is a dysregulated systemic immune response to infection that is responsible for ∼35% of in-hospital deaths at a significant fiscal health care cost. Our laboratory, among others, has demonstrated the efficacy of targeting negative checkpoint regulators (NCRs) to improve survival in a murine model of sepsis, cecal ligation and puncture (CLP). B7-CD28 superfamily member, V-domain Immunoglobulin Suppressor of T cell Activation (VISTA), is an ideal candidate for strategic targeting in sepsis. VISTA is a 35-45 kDa type 1 transmembrane protein with unique biology that sets it apart from all other NCRs...

Inhibitory immune receptors are important for maintaining immune homeostasis. We identified epigenetic alterations in two members of this group, LAIR1 and LAIR2, in lymphoma patients with inflammatory tissue damage and susceptibility to infection. We predicted that the expression of LAIR genes is controlled by immune mediators acting on transcriptional regulatory elements. Using flow cytometry, qRT-PCR, and RNAseq, we measured LAIR1 and LAIR2 in human and murine immune cell subsets at baseline and post-treatment with immune mediators, including type I and II interferons, tumor necrosis factor-alpha, and lipopolysaccharide (LPS)...

Candida albicans belongs to our commensal mucosal flora and in immune-competent individuals in the absence of epithelial damage, this fungus is well tolerated and controlled by our immune defense. However, C. albicans is an opportunistic microorganism that can cause different forms of infections, ranging from superficial to life-threatening systemic infections. C. albicans is polymorphic and switch between different phenotypes, e.g., from yeast form to hyphal form. C. albicans hyphae are invasive and can grow into tissues to eventually reach circulation...

Because granulomas are a hallmark of tuberculosis (TB) pathogenesis, the study of the dynamic changes in their cellular composition and morphological character can facilitate our understanding of TB pathogenicity. Adult zebrafish infected with Mycobacterium marinum (M. m) form granulomas that are similar to the granulomas in human TB patients and therefore have been used to study host-mycobacterium interactions. Most studies of zebrafish granulomas, however, have focused on necrotic granulomas, while a systematic description of the different stages of granuloma formation in the zebrafish model is lacking...

Tissue infiltration by circulating leukocytes via directed migration (also referred to as chemotaxis) is a common pathogenic mechanism of inflammatory diseases. G-protein coupled receptors (GPCRs) are essential for sensing chemokine gradients and directing the movement of leukocytes during immune responses. The TNF-α-induced protein 8-like (TIPE or TNFAIP8L) family of proteins are newly described pilot proteins that control directed migration of murine leukocytes. However, how leukocytes integrate site-specific directional cues, such as chemokine gradients, and utilize GPCR and TIPE proteins to make directional decisions are not well understood...

Myocarditis is an inflammatory heart disease that mostly affects young people. Myocarditis involves a complex immune network; however, its detailed pathogenesis is currently unclear. The diversity and plasticity of immune cells, either in the peripheral blood or in the heart, have been partially revealed in a number of previous studies involving patients and several kinds of animal models with myocarditis. It is the complexity of immune cells rather than one cell type that is the culprit. Thus, recognizing the individual intricacies within immune cells in the context of myocarditis pathogenesis and finding the key intersection of the immune network may help in the diagnosis and treatment of this condition...

The role of natural killer group 2D (NKG2D) in peripheral T cells as a costimulatory receptor is well established. However, its contribution to T cell thymic education and functional imprint is unknown. Here, we report significant changes in development, receptor signaling, transcriptional program, and function in T cells from mice lacking NKG2D signaling. In C57BL/6 (B6) and OT-I mice, we found that NKG2D deficiency results in Vβ chain usage changes and stagnation of the double-positive stage in thymic T cell development...

Breast cancer is the most prevalent malignant neoplasm worldwide, necessitating the development of novel therapeutic strategies owing to the limitations posed by conventional treatment modalities. Immunotherapy is an innovative approach that has demonstrated significant efficacy in modulating a patient's innate immune system to combat tumor cells. In the era of precision medicine, adoptive immunotherapy for breast cancer has garnered widespread attention as an emerging treatment strategy, primarily encompassing cellular therapies such as tumor-infiltrating lymphocyte therapy, chimeric antigen receptor T/NK/M cell therapy, T-cell receptor gene-engineered T-cell therapy, lymphokine-activated killer cell therapy, cytokine-induced killer cell therapy, natural killer cell therapy, and γδ T cell therapy, among others...

Gut dysbiosis is linked to Type 1 diabetes mellitus (T1D). Inulin, a prebiotic, modulates the gut microbiota, promoting beneficial bacteria that produce essential short-chain fatty acids for immune regulation. However, how inulin affects T1D remains uncertain. Using a streptozotocin-induced (STZ) mouse model, we studied inulin's protective effects. Remarkably, STZ+INU mice resisted T1D, with none developing the disease. They had lower blood glucose, reduced pancreatic inflammation, and normalized serum insulin compared to STZ+SD mice...

Staphylococcus aureus (S. aureus) strains that produce the toxin Panton-Valentine leukocidin (PVL; PVL-SA) frequently cause recurrent skin and soft tissue infections (SSTI). PVL binds to and kills human neutrophils, resulting in the formation of neutrophil extracellular traps, but the pathomechanism has not been extensively studied. Furthermore, it is unclear why some individuals colonized with PVL-SA suffer from recurring infections whereas others are asymptomatic. We thus aimed to (a) investigate how PVL exerts its pathogenicity on neutrophils and (b) identify factors that could help to explain the predisposition of patients with recurring infections...

In solid tumors, there are multiple barriers for a CAR T cell to surmount in order to reach the tumor site. For better understanding whether CAR T cells effectively infiltrate into tumor site and simultaneously, whether there are off-target effects, real-time monitoring technologies need to be established. Cell-based Positron Emission Tomography (PET) reporter genes have been developed to monitor engineered cells in living subjects. In this study, we reported the construction of a novel reporter gene ΔPSMA pending for monitoring CAR T cells using 68Ga-PSMA-617 a method for tracking the distribution of CAR T cells in vivo was developed...

Cystic fibrosis (CF) is a life-shortening genetic disorder, caused by mutations in the gene that encodes Cystic Fibrosis Transmembrane-conductance Regulator (CFTR), a cAMP-activated chloride and bicarbonate channel. Persistent neutrophilic inflammation is a major contributor to CF lung disease. However, how CFTR loss-of-function leads to excessive inflammation and its clinical sequela remains incompletely understood. In this study, neutrophils from F508del-CF and healthy control (HC) participants were compared for gene transcription...

Follicular helper T cells (Tfh) are a subset of CD4+ T cells that are fundamental to forming germinal centers, which are the primary sites of antibody affinity maturation and the proliferation of activated B cells. Tfh cells have been extensively studied over the past 10 years, especially regarding their roles in cancer genesis. This review describes the characteristics of normal Tfh cells and focuses on the emerging link between Tfh cells and lymphomagenesis. Advances in lymphoma genetics have substantially expanded our understanding of the role of Tfh cells in lymphomagenesis...

This writing serves as a commentary on the findings presented in the original manuscript by Yang et al. in 2023, published in the Journal of Leukocyte Biology (JLB). This commentary first summarizes the spatial-temporal dynamics of regulatory T-cells (T-reg) derived from mice (Tabula Muris Senis) of different ages (3M, 18M, and 24M) at different anatomical niches like lymph nodes and bone marrow. We also reported possible combinations of receptor-ligand interactions among T follicular regulatory cells (Tfr), T follicular helper cells (Tfr), and Germinal Centre (GC) B-cells, such as Calmodulin/Fas axis and PSGL-1/L-selectin axis...

Non-small cell lung cancer (NSCLC) is the most pervasive lung cancer subtype. Recent studies have shown that immune checkpoint inhibitors achieved favorable clinical benefits in resectable NSCLC; however, the associated mechanism remains unclear. The role of T cells in antitumor immunity has received considerable attention, while the antitumor effects of tumor-infiltrating B cells (TIBs) in NSCLC remain poorly understood. Here, we conducted a single-cell RNA-seq analysis of immune cells isolated from 12 patients with IIIA NSCLC to investigate B cell subtypes and their functions following neoadjuvant chemoimmunotherapy...

No abstract text is available yet for this article.

Primary Sjögren's disease (pSD, also referred to as Sjögren's syndrome) is an autoimmune disease that primarily occurs in women. In addition to exocrine gland dysfunction, pSD patients exhibit B cell hyperactivity. B cell-intrinsic TLR7 activation is integral to the pathogenesis of SLE, a disease that shares similarities with pSD. The role of TLR7-mediated B cell activation in pSD, however, remains poorly understood. We hypothesized that age-associated B cells (ABCs) were expanded in pSD and that TLR7-stimulated ABC subsets exhibited pathogenic features characteristic of disease...

Neutrophils are the most abundant, phenotypically heterogeneous, and exert detrimental or protective roles during anti-viral response. Dengue virus has been reported to activate neutrophils. However, the effect of the dengue virus on the neutrophil phenotypes, survival, and release of inflammatory secretome is yet to be understood. Herein, we investigated the effect of dengue virus serotype-2 (DV-2) on effector functions of naïve neutrophils and studied the impact of its secretome on different immune cells...

Pneumonia caused by Streptococcus pneumoniae is a leading cause of death worldwide. A growing body of evidence indicates that the successful treatment of bacterial infections results from synergy between antibiotic-mediated direct antibacterial activity and the host's immune defenses. However, the mechanisms underlying the protective immune responses induced by amoxicillin, a β-lactam antibiotic used as the first-line treatment of S. pneumoniae infections, have not been characterized. A better understanding of amoxicillin's effects on host-pathogen interactions might facilitate the development of other treatment options...