Active secretion of IL-33 from astrocytes is dependent on TMED10 and promotes central nervous system homeostasis.

Interleukin-33 (IL-33), secreted by astrocytes, regulates the synapse development in the spinal cord and hippocampus and suppresses autoimmune disease in the central nervous system (CNS). However, the mechanism of unconventional protein secretion of this cytokine remains unclear. In this study, we found that IFN-γ promotes the active secretion of IL-33 from astrocytes, and the active secretion of IL-33 from cytoplasm to extracellular space was dependent on interaction with transmembrane emp24 domain 10 (TMED10) via the IL-1 like cytokine domain in astrocytes.

HMGB1 from Astrocytes Promotes EAE by Influencing the Immune Cell Infiltration-Associated Functions of BMECs in Mice.

High mobility group box 1 (HMGB1) has been reported to play an important role in experimental autoimmune encephalomyelitis (EAE). Astrocytes are important components of neurovascular units and tightly appose the endothelial cells of microvessels by their perivascular endfeet and directly regulate the functions of the blood-brain barrier. Astrocytes express more HMGB1 during EAE while the exact roles of astrocytic HMGB1 in EAE have not been well elucidated.

HMGB1 Promotes the Release of Sonic Hedgehog From Astrocytes.

High mobility group box 1 protein (HMGB1) is known to be a trigger of inflammation in experimental autoimmune encephalomyelitis (EAE), an animal model of multiple sclerosis (MS). However, it may play a different role in some way. Here we investigated the effect of HMGB1 on promoting sonic hedgehog (shh) release from astrocytes as well as the possible signal pathway involved in it.

Allograft or Recipient ST2 Deficiency Oppositely Affected Cardiac Allograft Vasculopathy Differentially Altering Immune Cells Infiltration.

The role of IL-33/ST2 signaling in cardiac allograft vasculopathy (CAV) is not fully addressed. Here, we investigated the role of IL-33/ST2 signaling in allograft or recipient in CAV respectively using MHC-mismatch murine chronic cardiac allograft rejection model. We found that recipients ST2 deficiency significantly exacerbated allograft vascular occlusion and fibrosis, accompanied by increased F4/80 macrophages and CD3 T cells infiltration in allografts.

Extracellular HMGB1 Contributes to the Chronic Cardiac Allograft Vasculopathy/Fibrosis by Modulating TGF-β1 Signaling.

Cardiac allograft vasculopathy (CAV) charactered with aberrant remodeling and fibrosis usually leads to the loss of graft after heart transplantation. Our previous work has reported that extracellular high-mobility group box 1 (HMGB1) participated in the CAV progression via promoting inflammatory cells infiltration and immune damage. The aim of this study was to investigate the involvement of HMGB1 in the pathogenesis of CAV/fibrosis and potential mechanisms using a chronic cardiac rejection model in mice.

An Autocrine Circuit of IL-33 in Keratinocytes Is Involved in the Progression of Psoriasis.

IL-33 is constitutively expressed in the skin. Psoriasis is a common skin inflammatory disease. The roles of IL-33 in psoriasis have not been well-elucidated.

Plasmacytoid dendritic cell deficiency in neonates enhances allergic airway inflammation via reduced production of IFN-α.

Allergic asthma, a chronic inflammatory airway disease associated with type 2 cytokines, often originates in early life. Immune responses at an early age exhibit a Th2 cell bias, but the precise mechanisms remain elusive. Plasmacytoid dendritic cells (pDCs), which play a regulatory role in allergic asthma, were shown to be deficient in neonatal mice.

Gut Microbiota Reconstruction Following Host Infection with Blood-stage Plasmodium berghei ANKA Strain in a Murine Model.

Malaria remains a global health problem. The relationship between Plasmodium spp. and the gut microbiota as well as the impact of Plasmodium spp.

Toll-like receptor 2 deficiency promotes the generation of alloreactive Th17 cells after cardiac transplantation in mice.

The emergence of alloreactive Th17 cells that mediate allograft rejection has provided an impetus to understand the factors affecting the generation of Th17 cells in allograft transplantation. How toll-like receptor 2 (TLR2) signalling regulates the generation of Th17 cells upon alloantigen stimuli remains unclear. In this study, we used a mouse model of cardiac allograft transplantation to investigate whether TLR2 signalling influences the development of Th17 cells.

Glycyrrhizin attenuates hepatic ischemia-reperfusion injury by suppressing HMGB1-dependent GSDMD-mediated kupffer cells pyroptosis.

Gasdermin D (GSDMD), a genetic substrate for inflammatory caspases, plays a central role in pyroptosis of macrophages and release of interleukin‑1β (IL-1β), but was mainly referred to microbial infection. High mobility group box-1 (HMGB1), served as an alarm molecule during various pathological process, has been widely recognized to be involved in liver ischemia-reperfusion (I/R). Glycyrrhizin, a natural anti-inflammatory and antiviral triterpene in clinical use, was recently referred to have ability to prevent I/R induced liver injury by inhibiting HMGB1 expression and activity.

Glycyrrhizin alleviates Con A-induced hepatitis by differentially regulating the production of IL-17 and IL-25.

Glycyrrhizin, a triterpenoid compound, has been reported to be an anti-inflammatory agent for the treatment of a variety of inflammatory diseases including hepatitis. However, the mechanism by which glycyrrhizin inhibits inflammation is unclear. Using a Con A-induced hepatitis model in mice, we found that administration of glycyrrhizin ameliorates Con A-induced liver injury, which manifests as reduction in the production of inflammatory cytokines IFN-γ, IL-6 and IL-17, as well as serum alanine aminotransferase (ALT).

Lactate inhibits ATP6V0d2 expression in tumor-associated macrophages to promote HIF-2α-mediated tumor progression.

Macrophages perform key functions in tissue homeostasis that are influenced by the local tissue environment. Within the tumor microenvironment, tumor-associated macrophages can be altered to acquire properties that enhance tumor growth. Here, we found that lactate, a metabolite found in high concentration within the anaerobic tumor environment, activated mTORC1 that subsequently suppressed TFEB-mediated expression of the macrophage-specific vacuolar ATPase subunit ATP6V0d2.

CD8 T cell/IL-33/ILC2 axis exacerbates the liver injury in Con A-induced hepatitis in T cell-transferred Rag2-deficient mice.

Background: Previous studies showed that CD4 T cells play a critical role in Con A-induced hepatitis in wild-type mice. However, the role of CD8 T cells in the setting of Con A-induced hepatitis is enigmatic. The aim of study is to investigate the function of CD8 T cells in the context of Con-A-induced hepatitis.

Effects of mimicked acetylated HMGB1 on macrophages and dendritic cells.

Extracellular high mobility group box 1 (HMGB1) serves a critical role in inflammatory diseases. HMGB1 is released into the extracellular environment mainly by passive release from necrotic cells or active secretion from monocytes/macrophages following stimulation. However, the translocation of actively secreted HMGB1 from the nucleus to the cytoplasm with post‑translational modifications such as acetylation is required; HMGB1 is then released into the extracellular space.

Interleukin-33 deficiency exacerbated experimental autoimmune encephalomyelitis with an influence on immune cells and glia cells.

Interleukin (IL)-33, a member of the IL-1 cytokine family, is highly expressed in central nervous system (CNS), suggesting its potential role in CNS. Although some studies have focused on the role of IL-33 in multiple sclerosis (MS) / experimental autoimmune encephalomyelitis (EAE), an autoimmune disease characterized by demyelination and axonal damage in CNS, the exact role of IL-33 in MS/EAE remains unclear and controversial. Here, we used IL-33 knockout mice to clarify the role of endogenous IL-33 in EAE by simultaneously eliminating its role as a nuclear transcription factor and an extracellular cytokine.

Glycyrrhizin Protects Mice Against Experimental Autoimmune Encephalomyelitis by Inhibiting High-Mobility Group Box 1 (HMGB1) Expression and Neuronal HMGB1 Release.

The inflammatory mediator high-mobility group box 1 (HMGB1) plays a critical role in the pathogenesis of human multiple sclerosis (MS) and mouse experimental autoimmune encephalomyelitis (EAE). Glycyrrhizin (GL), a glycoconjugated triterpene extracted from licorice root, has the ability to inhibit the functions of HMGB1; however, GL's function against EAE has not been thoroughly characterized to date. To determine the benefit of GL as a modulator of neuroinflammation, we used an study to examine GL's effect on EAE along with primary cultured cortical neurons to study the GL effect on HMGB1 release.

LSECs express functional NOD1 receptors: A role for NOD1 in LSEC maturation-induced T cell immunity in vitro.

Liver sinusoidal endothelial cells (LSECs) are organ resident APCs capable of antigen presentation and subsequent tolerization of T cells under physiological conditions. In this study, we investigated whether LSEC pretreatment with NOD-like receptor (NLR) agonists can switch the cells from a tolerogenic to an immunogenic state and promote the development of T cell immunity. LSECs constitutively express NOD1, NOD2 and RIPK2.

Inhibition of autophagy with 3-methyladenine is protective in a lethal model of murine endotoxemia and polymicrobial sepsis.

Here, the regulatory role of autophagy is examined in both an LPS-induced lethal endotoxic shock mouse model and cecal ligation and puncture (CLP) mouse model. Autophagy-inhibitor 3-methyladenine (3-MA) and autophagy-enhancer rapamycin were administrated to mice challenged with LPS or CLP. Animals challenged with LPS or CLP combined with 3-MA displayed increased survival after endotoxemia, but LPS combined with rapamycin worsened the endotoxic shock of the mice.

Local Stimulation of Liver Sinusoidal Endothelial Cells with a NOD1 Agonist Activates T Cells and Suppresses Hepatitis B Virus Replication in Mice.

Functional maturation of liver sinusoidal endothelial cells (LSECs) induced by a NOD1 ligand (diaminopimelic acid [DAP]) during viral infection has not been well defined. Thus, we investigated the role of DAP-stimulated LSEC maturation during hepatitis B virus (HBV) infection and its potential mechanism in a hydrodynamic injection (HI) mouse model. Primary LSECs were isolated from wild-type C57BL/6 mice and stimulated with DAP in vitro and in vivo and assessed for the expression of surface markers as well as for their ability to promote T cell responses via flow cytometry.

GRP78 Impairs Production of Lipopolysaccharide-Induced Cytokines by Interaction with CD14.

The 78-kDa glucose-regulated protein (GRP78) is a stress-inducible chaperone that resides primarily in the endoplasmic reticulum. GRP78 has been described to be released at times of cellular stress and as having extracellular properties that are anti-inflammatory or favor the resolution of inflammation. In the current study, we confirmed that GRP78 impaired the production of lipopolysaccharide-induced pro-inflammatory cytokines in GRP78-treated bone-marrow-derived dendritic cells (DCs).

Down-regulation of nuclear HMGB1 reduces ischemia-induced HMGB1 translocation and release and protects against liver ischemia-reperfusion injury.

Hepatocyte-specific HMGB1 deletion has been found to worsen the injury and inflammation in liver ischemia-reperfusion injury (IRI), highlighting a role for intracellular HMGB1 in cellular protection. Down-regulation of nuclear HMGB1 by small interfering RNA (siRNA) might not only decrease its injurious extracellular role by reducing its release but also serve to maintain its beneficial intracellular role, thus protecting against IRI. We established a non-lethal liver IRI model in mice via segmental hepatic warm ischemia for 1 h and reperfusion for 6 h.

Glycyrrhizin ameliorates experimental colitis through attenuating interleukin-17-producing T cell responses via regulating antigen-presenting cells.

Glycyrrhizin, a component of Chinese medicine licorice root, has the ability to inhibit the functions of high-mobility group box 1 (HMGB1). While glycyrrhizin is known to have anti-inflammatory activities, the underlying mechanisms by which glycyrrhizin inhibits inflammation during the development of trinitrobenzenesulfonic acid (TNBS)-induced experimental colitis are not well understood. This study systemically examined the regulatory effects of glycyrrhizin on inflammatory response in TNBS-induced murine colitis and explored the potential mechanisms involved in this process.