Promoter methylation and increased expression of PD-L1 in patients with active tuberculosis.

The PD-1/PD-L1 pathway plays a pivotal role in T cell activity and is involved in the pathophysiology of (MTB) infection. DNA methylation is a mechanism that modulates PD-L1 expression in cancer cells. However, its effect on PD-L1 expression in macrophages after MTB infection remains unknown.

Surface TREM2 on circulating M-MDSCs as a novel prognostic factor for adults with treatment-naïve diffuse large B-cell lymphoma.

Introduction: Circulating monocytic myeloid-derived suppressive cells (M-MDSCs) are implicated as a poor prognostic factor and cause CAR T-cell failure in diffuse large B-cell lymphoma (DLBCL). Triggering receptors expressed on myeloid cells 2 (TREM2) are a transmembrane glycoprotein that polarize macrophages to anti-inflammation phenotype but have never been explored on M-MDSCs. This study aims to elucidate the expression and clinical impact of surface TREM2 on circulating M-MDSCs derived from DLBCL adults.

Decoy Receptor 3 Suppresses T-Cell Priming and Promotes Apoptosis of Effector T-Cells in Acute Cell-Mediated Rejection: The Role of Reverse Signaling.

Background: Decoy receptor 3 (DcR3) belongs to the tumor necrosis factor (TNF) receptor superfamily and neutralizes TNF ligands, including FasL and TRAIL, to prevent T activation during T-cell priming. However, the cellular mechanisms underlying acute cell-mediated rejection (ACMR) remain unknown.

Methods: We generated DcR3 transgenic (Tg) mice and mice with high DcR3 expression (HDE) to study both and .

TREM-2 mediates dendritic cell-induced NO to suppress Th17 activation and ameliorate chronic kidney diseases.

Chronic kidney disease (CKD) is a global public health issue. CKD is caused by the infiltration of various myeloid cell types into renal tissue, resulting in renal fibrosis and tubular atrophy. Unilateral ureteral obstruction (UUO) surgery in mice is a model of CKD and characterized by high expression of the anti-inflammatory receptor, Triggering receptor expressed on myeloid cells 2 (TREM-2), on myeloid cells in affected kidneys.

PD-L1 Expression in Monocytes Correlates with Bacterial Burden and Treatment Outcomes in Active Pulmonary Tuberculosis.

The PD-1/PD-L1 pathway is critical in T cell biology; however, the role of the PD-1/PD-L1 pathway in clinical characteristics and treatment outcomes in pulmonary tuberculosis (PTB) patients is unclear. We prospectively enrolled PTB, latent TB infection (LTBI), and non-TB, non-LTBI subjects. The expression of PD-1/PD-L1 on peripheral blood mononuclear cells (PBMCs) was measured and correlated with clinical characteristics and treatment outcomes in PTB patients.

Galectin-3 promotes noncanonical inflammasome activation through intracellular binding to lipopolysaccharide glycans.

Cytosolic lipopolysaccharides (LPSs) bind directly to caspase-4/5/11 through their lipid A moiety, inducing inflammatory caspase oligomerization and activation, which is identified as the noncanonical inflammasome pathway. Galectins, β-galactoside-binding proteins, bind to various gram-negative bacterial LPS, which display β-galactoside-containing polysaccharide chains. Galectins are mainly present intracellularly, but their interactions with cytosolic microbial glycans have not been investigated.

Hypoxic mesenchymal stem cells ameliorate acute kidney ischemia-reperfusion injury via enhancing renal tubular autophagy.

Background: Acute kidney injury (AKI) is an emerging global healthcare issue without effective therapy yet. Autophagy recycles damaged organelles and helps maintain tissue homeostasis in acute renal ischemia-reperfusion (I/R) injury. Hypoxic mesenchymal stem cells (HMSCs) represent an innovative cell-based therapy in AKI.

Efficient conversion of human induced pluripotent stem cells into microglia by defined transcription factors.

Microglia, the immune cells of the central nervous system, play critical roles in brain physiology and pathology. We report a novel approach that produces, within 10 days, the differentiation of human induced pluripotent stem cells (hiPSCs) into microglia (iMG) by forced expression of both SPI1 and CEBPA. High-level expression of the main microglial markers and the purity of the iMG cells were confirmed by RT-qPCR, immunostaining, and flow cytometry analyses.

An oral absorbent, AST-120, restores vascular growth and blood flow in ischemic muscles in diabetic mice via modulation of macrophage transition.

Background Diabetes has a pronounced effect on the peripheral vasculature. The accumulation of advanced glycation end products (AGEs) is regarded as the crucial mechanism responsible for vascular damage in diabetes, but it is not easy to be avoided from food. In this study, we aimed to investigate the effects of an oral absorbent, AST-120, on the accumulation of AGEs and changes in blood flow recovery in diabetic mice.

TREM-1 enhances Mycobacterium tuberculosis-induced inflammatory responses in macrophages.

Triggering receptor expressed on myeloid cells 1 (TREM-1) extensively interacts with toll-like receptors and amplifies pro-inflammatory responses. The effect of TREM-1 on Mycobacterium tuberculosis (MTB)-related immune responses remains to be elucidated. We isolated bone marrow-derived macrophages (BMDMs) from wild-type mice and Trem-1 KO mice and treated them with MTB whole cell lysate and EsxA (ESAT-6).

Trichostatin A Alleviates Renal Interstitial Fibrosis Through Modulation of the M2 Macrophage Subpopulation.

Mounting evidence indicates that an increase in histone deacetylation contributes to renal fibrosis. Although inhibition of histone deacetylase (HDAC) can reduce the extent of fibrosis, whether HDAC inhibitors exert the antifibrotic effect through modulating the phenotypes of macrophages, the key regulator of renal fibrosis, remains unknown. Moreover, the functional roles of the M2 macrophage subpopulation in fibrotic kidney diseases remain incompletely understood.

Nintedanib Reduces Neutrophil Chemotaxis via Activating GRK2 in Bleomycin-Induced Pulmonary Fibrosis.

Neutrophils are involved in the alveolitis of idiopathic pulmonary fibrosis (IPF). However, their pathogenic mechanisms are still poorly understood. Nintedanib has antifibrotic and anti-inflammatory activity in IPF.

Upregulation of RelB in the miR-122 knockout mice contributes to increased levels of proinflammatory chemokines/cytokines in the liver and macrophages.

Objective: MicroRNA-122 (miR-122) is the most abundant miRNA in the liver and it plays an important role in regulating liver metabolism and tumor formation. Previous studies also reveal an anti-inflammatory function of miR-122; however, relatively little is known about the mechanisms by which miR-122 suppresses inflammation. This study aims to search the effect of miR-122 on proinflammatory chemokines/cytokines production in mice.

Vaccine adjuvant activity of a TLR4-activating synthetic glycolipid by promoting autophagy.

Toll-like receptors (TLRs) play crucial roles in host immune defenses. Recently, TLR-mediated autophagy is reported to promote immune responses via increasing antigen processing and presentation in antigen presenting cells. The present study examined whether the synthetic TLR4 activator (CCL-34) could induce autophagy to promote innate and adaptive immunity.

Mitochondrial oxidative stress by Lon-PYCR1 maintains an immunosuppressive tumor microenvironment that promotes cancer progression and metastasis.

Mitochondrial Lon is a chaperone protein whose upregulation increases the production of mitochondrial reactive oxygen species (ROS). However, there is a lack of information in detail on how mitochondrial Lon regulates cancer metastasis through ROS production in the tumor microenvironment (TME). Our results show that elevated Lon promotes epithelial-mesenchymal transition (EMT) via ROS-dependent p38 and NF-κB-signaling.

TREM-1-dependent M1 macrophage polarization restores intestinal epithelium damaged by DSS-induced colitis by activating IL-22-producing innate lymphoid cells.

Background: Triggering receptor expressed on myeloid cells-1 (TREM-1) is highly expressed on macrophages in inflamed intestines and reportedly promotes inflammatory bowel disease (IBD) by augmenting pro-inflammatory responses. To study the mechanism mediated by TREM-1 on macrophages, we generated an independent TREM-1 deficient mouse.

Methods: Acute colitis was induced in C57BL/6 and TREM-1-deficient mice by the administration of dextran sodium sulfate (DSS).

Induced Pluripotent Stem Cells Regulate Triggering Receptor Expressed on Myeloid Cell-1 Expression and the p38 Mitogen-Activated Protein Kinase Pathway in Endotoxin-Induced Acute Lung Injury.

Induced pluripotent stem cells (iPSCs) can attenuate the pathological severity and neutrophil migration of lipopolysaccharide (LPS)-induced acute lung injury (ALI). However, interactions that may occur between iPSCs and the triggering receptor expressed on myeloid cells (TREM) family of proteins remain unclear. In this study, murine iPSCs (miPSCs) were delivered via tail vein injection to wild type, TREM-1 knockout (KO), and TREM-2 KO C57BL/6 mice 4 hours after an intratracheal delivery of LPS.

Role of TREM-1 in pulmonary tuberculosis patients- analysis of serum soluble TREM-1 levels.

Triggering receptor expressed on myeloid cells 1 (TREM-1) amplifies inflammatory responses and is upregulated during sepsis and pulmonary infection. The association between serum soluble TREM-1 (sTREM-1) level and pulmonary tuberculosis (PTB) disease deserves investigation. In the present study, patients with PTB, latent TB infection (LTBI), and non-TB, non-LTBI subjects were prospectively enrolled and serum levels of sTREM-1, sTREM-2, and C-reactive protein (CRP) were measured.

CLEC9A modulates macrophage-mediated neutrophil recruitment in response to heat-killed Mycobacterium tuberculosis H37Ra.

Tuberculosis is a fatal human infectious disease caused by Mycobacterium tuberculosis (M. tuberculosis) that is prevalent worldwide. Mycobacteria differ from other bacteria in that they have a cell wall composed of specific surface glycans that are the major determinant of these organisms' pathogenicity.

Triggering receptor expressed on myeloid cells-1 (TREM-1) deficiency augments BAFF production to promote lupus progression.

Sensing of nucleic acids by pattern recognition receptors is the key for the initiation and development of systemic lupus erythematosus (SLE). Triggering receptor expressed on myeloid cells-1 (TREM-1) is a novel innate immune receptor, which can amplify Toll-like receptor (TLR)-induced inflammatory responses. Although patients with lupus exhibit increased serum levels of soluble TREM-1 (sTREM-1), the role of TREM-1 in SLE remains unknown.

Attenuation of Tubular Injury and Renal Fibrosis by TI-HU-YIN via Reduction in Transforming Growth Factor-β1 Expression in Unilateral Ureteral Obstruction Mice.

TI-HU-YIN (JCKD), a compound composed of many Chinese herbs, is hypothesized to attenuate renal tubular injury and interstitial fibrosis. Moreover, its renoprotective effects were assessed in animal and in vitro studies. First, male C57BL/6 mice were under sham operation or unilateral ureteral obstruction (UUO) surgery, and then treated with phosphate buffer solution (PBS), aliskirin and valsartan (A+V), and JCKD for 14 days.

Expression of decoy receptor 3 in kidneys is associated with allograft survival after kidney transplant rejection.

Decoy receptor 3 (DcR3) expression in kidneys has been shown to predict progression of chronic kidney disease. We prospectively investigated a cohort comprising 96 renal transplant recipients (RTRs) undergoing graft kidney biopsies. Computer-assisted quantitative immunohistochemical staining value of DcR3 in renal tubular epithelial cells (RTECs) was used to determine the predictive role of DcR3 in kidney disease progression.

Polyubiquitination of Transforming Growth Factor β-activated Kinase 1 (TAK1) at Lysine 562 Residue Regulates TLR4-mediated JNK and p38 MAPK Activation.

Toll-like receptor 4 (TLR4) plays an important role in innate immunity by eliciting inflammation. Upon receptor engagement, transforming growth factor β-activated kinase 1 (TAK1) is an essential mediator that transmits a signal from the receptor to downstream effectors, IκB kinase (IKK) and the mitogen-activated protein kinases (MAPKs), which control the production of inflammatory cytokines. However, the association between phosphorylation and ubiquitination of TAK1 is not yet clear.