Leptin Receptor Deficiency Impairs Lymph Node Development and Adaptive Immune Response.

Activation and clonal expansion of the Ag-specific adaptive immune response in the draining lymph node is essential to clearing influenza A virus infections. Activation sufficient for virus clearance is dependent on the lymph node's architectural organization that is maintained by stromal cells, chiefly fibroblastic reticular cells. During an analysis of influenza A virus clearance in leptin receptor knockout (DB/DB) mice, we observed that the DB/DB mice have markedly reduced numbers of lymph node fibroblastic reticular cells at the steady state.

Bone marrow stromal cell antigen-1 deficiency protects from acute kidney injury.

This study aimed to investigate the role of bone marrow stromal cell antigen-1 (Bst1; also known as CD157) in acute kidney injury (AKI). Bst1 is a cell surface molecule with various enzymatic activities and downstream intracellular signaling pathways that modulate the immune response. Previous research has linked Bst1 to diseases such as ovarian cancer, Parkinson's disease, and rheumatoid arthritis.

CCR2 monocytes as therapeutic targets for acute disc herniation and radiculopathy in mouse models.

Objective: Back pain and radiculopathy caused by disc herniation are major health issues worldwide. While macrophages are key players in disc herniation induced inflammation, their roles and origins in disease progression remain unclear. We aim to study the roles of monocytes and derivatives in a mouse model of disc herniation.

Tfh cells with NLRP3 inflammasome activation are essential for high-affinity antibody generation, germinal centre formation and autoimmunity.

Objective: NLRP3 inflammasome regulates T cell responses. This study examined the roles of NLRP3 inflammasome activation in the regulation of T follicular helper (Tfh) cells during humoral response to T dependent antigens and in systemic lupus erythematosus (SLE).

Methods: NLRP3 inflammasome activation of Tfh cells was studied in B6, MRL/lpr and NZM2328 mice and in SLE patients and healthy controls using a fluorescence-labelled caspase-1 inhibitor probe.

Cyclic swelling enabled, electrically conductive 3D porous structures for microfluidic urinalysis devices.

Urinalysis is a simple and non-invasive approach for the diagnosis and monitoring of organ health and also is often used as a facile technique in assessment of substance abuse. However, quantitative urinalysis is predominantly limited to clinical laboratories. Here, we present an electrical sensing based, reusable, cellular microfluidic device that offers a fast urinalysis through quantitative reading of the electrical signals.

Heterogeneous macrophages contribute to the pathology of disc herniation induced radiculopathy.

Background Context: Macrophages play important roles in the progression of intervertebral disc herniation and radiculopathy.

Purpose: To better understand the roles of macrophages in this process, we developed a new mouse model that mimics human radiculopathy.

Study Design/setting: A preclinical randomized animal study.

Co-immunostaining of ICAM-1, ICAM-2, and CD31 in Mouse Kidney Glomeruli.

Glomerulonephritis (GN) is a common pathological condition in chronic kidney diseases that often leads to end stage renal failure. Mac-1 (CD11b/CD18)-mediated neutrophil, macrophage, and dendritic cell glomerular infiltration leading to cellular dysfunction and destruction is an important disease mechanism. The cellular distribution and dynamics of the expression of Mac-1 ligands ICAM-1 and ICAM-2 in GN have not been well studied because of the difficulties in tissue staining and colocalizing glomerular cells with surface antigens.

Autoimmune experimental orchitis and chronic glomerulonephritis with end stage renal disease are controlled by Cgnz1 for susceptibility to end organ damage.

Cgnz1 on chromosome 1 mapped into a 1.34 Mb region of chromosome 1 in NZM2328 confers the progression of immune complex (IC)-mediated glomerulonephritis (GN) from acute GN (aGN) to chronic GN (cGN) with severe proteinuria and end stage renal disease in female mice. This genetic locus mediates podocyte susceptibility to IC-mediated damage.

A novel immunofluorescence detection method for renal cell-type specific in situ cytokine production by confocal microscopy.

The detection of cytokines production in tissues is subjected to significant limitations: (1) Cytokine protein production frequently does not correlate with mRNA levels. (2) Cytokines are secreted rapidly and dissipate from the cellular source, thus making detection difficult. (3) The synthetic rate of many cytokines are low.

Circulating fibrocytes traffic to the lung in murine acute lung injury and predict outcomes in human acute respiratory distress syndrome: a pilot study.

Background: Fibrosis is an integral component of the pathogenesis of acute lung injury and is associated with poor outcomes in patients with acute respiratory distress syndrome (ARDS). Fibrocytes are bone marrow-derived cells that traffic to injured tissues and contribute to fibrosis; hence their concentration in the peripheral blood has the potential to serve as a biomarker of lung fibrogenesis. We therefore sought to test the hypothesis that the concentration and phenotype of circulating fibrocytes in patients with ARDS predicts clinical outcomes.

Interactions among glomerulus infiltrating macrophages and intrinsic cells via cytokines in chronic lupus glomerulonephritis.

Inflammation plays a key role in the pathogenesis of lupus nephritis (LN) and inflammatory cytokines within the glomeruli are critical in this process. However, little information is available for the identities of the cell types that are primarily responsible for the production and function of the various cytokines. We have devised a novel method to visualize cytokine signals in the kidney by confocal microscopy and found that cytokine production within the glomerulus is cell type-specific and under translational control.

Perivascular CD73 cells attenuate inflammation and interstitial fibrosis in the kidney microenvironment.

Progressive tubulointerstitial fibrosis may occur after acute kidney injury due to persistent inflammation. Purinergic signaling by 5'-ectonucleotidase, CD73, an enzyme that converts AMP to adenosine on the extracellular surface, can suppress inflammation. The role of CD73 in progressive kidney fibrosis has not been elucidated.

Monocyte-Derived Dendritic Cells as Antigen-Presenting Cells in T-Cell Proliferation and Cytokine Production.

Dendritic cells (DC) are the most potent antigen-presenting cells that link innate with adaptive immunity. They circulate the body and sample the microenvironments for maintaining homeostasis and for mounting T-cell responses against invading pathogens, foreign antigens, and aberrant self-proteins. In humans, DC derived from blood monocytes (MDC) by cytokine treatment provide the most abundant and versatile source for studying DC and T-cell biology, and for use as adjuvants in cancer therapy.

IL233, an IL-2-IL-33 hybrid cytokine induces prolonged remission of mouse lupus nephritis by targeting Treg cells as a single therapeutic agent.

Lupus glomerulonephritis (GN) is an autoimmune disease characterized by immune complex-deposition, complement activation and glomerular inflammation. In lupus-prone NZM2328 mice, the occurrence of lupus GN was accompanied by a decrease in Treg cells and an increase in proinflammatory cytokine-producing T cells. Because IL-33 in addition to IL-2 has been shown to be important for Treg cell proliferation and ST2 (IL-33 receptor) positive Treg cells are more potent in suppressor activity, a hybrid cytokine with active domains of IL-2 and IL-33 was generated to target the ST2 Treg cells as a therapeutic agent to treat lupus GN.

Leukotriene A4 Hydrolase Activation and Leukotriene B4 Production by Eosinophils in Severe Asthma.

Asthma is associated with the overproduction of leukotrienes (LTs), including LTB4. Patients with severe asthma can be highly responsive to 5-lipoxygenase (5-LO) inhibition, which blocks production of both the cysteinyl LTs and LTB4. Production of LTB4 has traditionally been ascribed to neutrophils, mononuclear phagocytes, and epithelial cells, and acts as a chemoattractant for inflammatory cells associated with asthma.

Podocyte Activation of NLRP3 Inflammasomes Contributes to the Development of Proteinuria in Lupus Nephritis.

Objective: Development of proteinuria in lupus nephritis (LN) is associated with podocyte dysfunction. The NLRP3 inflammasome has been implicated in the pathogenesis of LN. The purpose of this study was to investigate whether NLRP3 inflammasome activation is involved in the development of podocyte injury in LN.

Dependence of Glomerulonephritis Induction on Novel Intraglomerular Alternatively Activated Bone Marrow-Derived Macrophages and Mac-1 and PD-L1 in Lupus-Prone NZM2328 Mice.

Glomerular damage mediated by glomerulus-infiltrating myeloid-derived cells is a key pathogenic event in lupus nephritis (LN), but the process is poorly understood. Confocal microscopy of kidney sections and flow cytometry analysis of glomerular cells from magnetic bead-purified glomeruli have identified glomerulus-infiltrating leukocyte populations in NZM2328 (NZM) lupus-prone mice with spontaneous chronic glomerulonephritis (GN) and anti-glomerular basement membrane-induced nephritis. The occurrence of a major glomerulus-infiltrating CD11bF4/80I-A macrophage population exhibiting the markers programmed death ligand-1 (PD-L1), Mac-2, and macrophage mannose receptor (CD206) and producing , , , , and mRNA, which are known to be expressed by alternatively activated (M2b) macrophages, correlated with proteinuria status.

Cross-Presentation of Soluble and Cell-Associated Antigen by Murine Hepatocytes Is Enhanced by Collectrin Expression.

Cross-presentation is a modular series of intracellular events dictating the internalization and subsequent MHC class I (MHC I) display of extracellular Ags. This process has been defined in dendritic cells and plays a fundamental role in the induction of CD8 T cell immunity during viral, intracellular bacterial, and antitumor responses. Herein, acute viral infection of murine liver with adenovirus, a model for intrahepatic cross-presentation, confirms hepatocytes directly contribute to cross-presentation of Ags and priming the pool of naive CD8 T cells within the liver microenvironment.

Endothelial Sphingosine 1‑Phosphate Receptor‑1 Mediates Protection and Recovery from Acute Kidney Injury.

Epithelial and endothelial injury and a cascade of immune and interstitial cell activation in the kidney lead to AKI. After mild to moderate AKI, the epithelium can regenerate and restore kidney function, yet little is known about the endothelium during these repair processes. Sphingosine 1-phosphate receptor 1 (S1P1), a G protein-coupled receptor, is necessary for vascular homeostasis.

Expression of scavenger receptor-AI promotes alternative activation of murine macrophages to limit hepatic inflammation and fibrosis.

Unlabelled: The liver maintains an immunologically tolerant environment as a result of continuous exposure to food and bacterial constituents from the digestive tract. Hepatotropic pathogens can take advantage of this niche and establish lifelong chronic infections causing hepatic fibrosis and hepatocellular carcinoma. Macrophages (Mϕ) play a critical role in regulation of immune responses to hepatic infection and regeneration of tissue.

Proximal Tubule CD73 Is Critical in Renal Ischemia-Reperfusion Injury Protection.

CD73-derived adenosine plays an anti-inflammatory role in various organs. However, its role in renal ischemia-reperfusion injury (IRI) is controversial. We targeted CD73 mutant mice to determine the function of CD73 expressed by various renal cell types under mild IRI conditions.

Murine liver-resident group 1 innate lymphoid cells regulate optimal priming of anti-viral CD8+ T cells.

The liver contains 2 transcriptionally distinct group 1 ILC subsets: CD49a ILC1s and CD49b NK cells. However, little is known about how group 1 ILCs contribute to hepatic immune responses. Therefore, we characterized murine liver-resident group 1 ILCs and found that CD49a ILC1s express high levels of the inhibitory receptor NKG2A and localize near DCs in perivascular spaces surrounding the portal triads.