Journal of Leukocyte Biology

Human monocyte-derived dendritic cells (moDCs) develop from monocytes play a key role in innate inflammatory responses as well as T-cell priming. Steady-state moDCs regulate immunogenicity and tolerogenicity by changing metabolic patterns to participate in the body's immune response. Increased glycolytic (Gly) metabolism after danger signal induction may strengthen moDCs' immunogenicity, whereas high levels of mitochondrial oxidative phosphorylation (OXPHOS) were associated with the immaturity and tolerogenicity of moDCs...

The calcium (Ca2+) permeable transient receptor potential vanilloid 4 (TRPV4) cation channel is expressed in neutrophils and contributes to myocardial ischemia/reperfusion (I/R) injury. Here we tested the hypotheses that TRPV4 promotes neutrophil activation and subsequently aggregates myocardial I/R injury. TRPV4 protein was confirmed in neutrophils and its function was assessed by the current and intracellular Ca2+ concentration elevations evoked by TRPV4 agonists. Furthermore, TRPV4 agonists dose-repandly promoted migration toward fMLP, reactive oxygen species (ROS) production, and myeloperoxidase (MPO) release, which were prevented by pretreatment with a selective TRPV4 antagonist, in neutrophils from TRPV4 knock-out (KO) mice, Ca2+-free medium, or BAPTA-AM + Ca2+-free medium...

Eosinophils are present in the thymus of mammals, yet their function at this site during homeostatic development is unknown. We used flow cytometry to determine the abundance and phenotype of eosinophils (here defined as SSchigh SiglecF+ CD11b+ CD45+ cells) in the thymus of mice during the neonatal period, the later postnatal period and into adulthood. We show that both the total number of thymic eosinophils and their frequency amongst leukocytes increase over the first two weeks of life, and that their accumulation in the thymus is dependent on the presence of an intact bacterial microbiota...

Cytokine-mediated mast cell regulation enables precise optimization of their own pro-inflammatory cytokine production. During allergic inflammation, Interleukin(IL)-4 regulates mast cell functions, tissue-homing and proliferation, but the direct role of closely related IL-13 for mast cell activation remains unclear. Previous work has shown that mast cells are potent IL-13 producers, but here we show that mouse mast cells do not directly respond to IL-13 by Stat6 activation, as they do not express measurable amount of IL-13Rα1 mRNA...

Inorganic polyphosphates are evolutionarily conserved bioactive phosphate polymers found as various chain lengths in all living organisms. In mammals, polyphosphates play a vital role in the regulation of cellular metabolism, coagulation, and inflammation. Long-chain polyphosphates are found along with endotoxins in pathogenic gram-negative bacteria and can participate in bacterial virulence. We aimed to investigate, whether exogenously administered polyphosphates modulate human leukocyte function in vitro by treating the cells with three different chain lengths of polyphosphates (P14, P100, and P700)...

More immune-related adverse events (irAEs) have emerged along with increased immune checkpoint inhibitors (ICIs) treatment. ICIs-induced myocarditis is a rare type of irAEs with early onset, rapid progression and high mortality. Its specific pathophysiological mechanism is not fully understood. Totally 46 patients with tumor and 16 ICI-induced myocarditis were included. We performed single cell RNA sequencing (scRNA-seq) on CD3+T cells, flow cytometry, plasma analysis of proteomics and lipidomics to improve our understanding of the disease...

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OBJECTIVES: Systemic juvenile idiopathic arthritis (sJIA) is a chronic pediatric inflammatory disease of unknown etiology, characterized by fever, rash, hepatosplenomegaly, serositis and arthritis. We hypothesized that intercellular communication, mediated by extracellular vesicles (EVs), contributes to sJIA pathogenesis and that the number and cellular sources of EVs would differ between inactive and active states of sJIA and healthy controls. METHODS: We evaluated plasma from healthy pediatric controls and sJIA patients with active systemic flare or inactive disease...

Inflammation plays a significant role in lung infection including that caused by Mycobacterium tuberculosis (M.tb), where both adaptive and innate lymphocytes can affect infection control. How inflammation affects infection is understood in a broad sense, including inflammaging (chronic inflammation) seen in the elderly, but the explicit role that inflammation can play in regulation of lymphocyte function is not known. To fill this knowledge gap, we used an acute lipopolysaccharide (LPS) treatment in young mice and studied lymphocyte responses, focusing on CD8 T cell subsets...

Hematopoiesis is a highly orchestrated biological process sustaining the supply of leukocytes involved in the maintenance of immunity, O2 and CO2 exchange, and wound healing throughout the life-time of an animal including human. During early hematopoietic cell development, several waves of hematopoiesis require the precise regulation of hematopoietic ontogeny as well as the maintenance of hematopoietic stem and progenitor cells (HSPCs) in the hematopoietic tissues, such as the fetal liver and bone marrow (BM)...

Macrophages play a critical role in ankylosing spondylitis (AS) by promoting autoimmune tissue inflammation through various effector functions. The inflammatory potential of macrophages is highly influenced by their metabolic environment. Here, we demonstrate that glycolysis is linked to the pro-inflammatory activation of human blood monocyte-derived macrophages (MDMs) in AS. Specifically, AS macrophages produced excessive inflammation, including TNFα, IL1β, and IL23, and displayed an overactive status by exhibiting stronger co-stimulatory signals, such as CD80, CD86, and HLA-DR...

DNA sensor proteins play an important role in transducing DNA signals to induce immune responses that initiate inflammation or clear pathogens. It has been previously shown that several DNA sensors are involved in regulating tumor biology and/or cancer immunology. However, a systemic analysis of DNA sensor expression and its correlation with prognosis has not been conducted. Here, we analyzed mRNA expression and protein abundance in liver cancer databases and found that the genes of five DNA sensors (POLR3A, PRKDC, DHX9, cGAS, and MRE11) were consistently upregulated in tumor tissue...

Asthma is the chronic pulmonary inflammatory response that could lead to respiratory failure when allergic reactions exacerbate. It is featured by type 2 immunity with eosinophilic inflammation, mucus and IgE production, and Th2 cytokine secretion upon repeated challenge of allergens. The symptom severity of asthma displays an apparent circadian rhythm with aggravated airway resistance in the early morning in patients. Bmal1 is the core regulator of the circadian clock, while the regulatory role of Bmal1 in asthma remains unclear...

Macrophages are an abundant cell population in the placenta and developing embryo and appear to be involved in processes of vascularisation, morphogenesis, organogenesis and hematopoiesis. The proliferation, differentiation and survival is dependent upon signals from the macrophage colony-stimulating factor receptor, CSF1R. Aside from the role in macrophages, Csf1r mRNA is highly-expressed in placental trophoblasts. To explore the function of macrophages and Csf1r in placental and embryonic development, we analysed the impact of homozygous Csf1r null mutation (Csf1rko) in the rat...

Type 3 innate lymphocytes (ILC3s) have recently been reported as key factors in inflammatory diseases, however, their role in viral myocarditis is unclear. By flow cytometry, CVB3 (Coxsachievirus B3)-induced myocarditis mice were detected to increase the number of ILC3s, and their main type was NKp46 + ILC3. In contrast, application of CD90.2 neutralizing antibody in T-cell-deficient mice reduced the number of ILCs and improved myocarditis. ILCs from CD45.1 mouse intestinal lamina propria lymphocytes were adoptively transferred into recipient mice, and a comparable proportion of CD45...

Mast cells are leukocytes that mediate various aspects of immunity and drive allergic hypersensitivity pathologies. Mast cells differentiate from hematopoietic progenitor cells in a manner that is largely IL-3 dependent. However, molecular mechanisms, including the signaling pathways that control this process, have yet to be thoroughly investigated. Here, we examine the role of the ubiquitous and critical MAPK signaling pathway due to its position downstream of the IL-3 receptor. Hematopoietic progenitor cells were harvested from the bone marrow of C57BL/6 mice and differentiated to bone marrow-derived mast cells (BMMCs) in the presence of IL-3 and MAPK inhibitors...

New strategies targeting stimulator of interferon genes (STING) proteins appear promising for eliciting immunotherapeutic responses. Activation of the STING pathway under the right circumstances can drive dendritic cell maturation, antitumor macrophage differentiation, T cell initiation and activation, natural killer cell activation, vascular reprogramming and/or cancer cell death, leading to immune-mediated tumor elimination and generation of antitumor immune memory. However, activation of the STING signaling pathway is complicated in tumor immunity...

Sjögren's syndrome (SS) is a systemic autoimmune disease characterized by dysfunction of the affected exocrine glands. Lymphocytic infiltration within the inflamed glands and aberrant B cell hyperactivation are the two salient pathological features in SS. Increasing evidence indicates that salivary gland (SG) epithelial cells act as a key regulator in the pathogenesis of SS, as revealed by the dysregulated innate immune signaling pathways in SG epithelium and increased expression of various proinflammatory molecules as well as their interaction with immune cells...

Chitin is a highly abundant N-acetyl-glucosamine (GlcNAc) polysaccharide which has been linked to immune responses in the context of fungal infections and allergic asthma, especially to T helper 2 (Th2) immune responses. Unfortunately, due to the frequent use of crude chitin preparations of unknown purity and degree of polymerization, there is still great uncertainty how chitin activates different parts of the human immune system. We recently identified chitin oligomers of six GlcNAc units as the smallest immunologically active chitin motif and the innate immune receptor TLR2 as a primary chitin sensor on human and murine myeloid cells, but the response of further immune cells, e...

Antiretroviral therapy (ART) has been effective in suppressing HIV viral load and enabling people living with HIV (PLWH) to experience longer, more conventional lives. However, as PLWH are living longer, they are developing aging-related diseases prematurely and are more susceptible to comorbidities that have been linked to chronic inflammation. Coincident with HIV infection and aging, drug abuse has also been independently associated with gut dysbiosis, microbial translocation, and inflammation. Here, we hypothesized that injection drug use (IDU) would exacerbate HIV-induced immune activation and inflammation, thereby intensifying immune dysfunction...