LGR4 Deficiency Aggravates Skin Inflammation and Epidermal Hyperplasia in Imiquimod-Induced Psoriasis.

Psoriasis is a chronic inflammatory skin disease characterised by inflammatory cell infiltration, keratinocyte hyperproliferation and increased neovascularization. Despite extensive research, the precise mechanisms underlying psoriasis pathology and treatment strategies remain unclear because of a complex aetiology and disease progression. Hence, in this study, we aimed to identify potential therapeutic targets for psoriasis and explore their effects on disease progression.

FFAR2 expressing myeloid-derived suppressor cells drive cancer immunoevasion.

Background: Emerging evidences suggest that aberrant metabolites contributes to the immunosuppressive microenvironment that leads to cancer immune evasion. Among tumor immunosuppressive cells, myeloid-derived suppressor cells (MDSCs) are pathologically activated and extremely immunosuppressive, which are closely associated with poor clinical outcomes of cancer patients. However, the correlation between MDSCs mediated immunosuppression and particular cancer metabolism remained elusive.

Identification and characterization of colorectal-cancer-associated SNPs on the SMAD7 locus.

Purpose: Genome-wide association studies have identified SMAD7 as a colorectal cancer (CRC) susceptibility gene. However, its underlying mechanism has not yet been characterized. This study screened functional SNPs (fSNPs) related to colorectal cancer through Reel-seq and obtained regulatory proteins on functional SNPs.

LIGHT/TNFSF14 promotes CAR-T cell trafficking and cytotoxicity through reversing immunosuppressive tumor microenvironment.

Tertiary lymphoid structures (TLSs) in tumor tissues facilitate immune cell trafficking and cytotoxicity, which benefits survival and favorable responses in immune therapy. Here, we observed a high correlation of tumor necrosis factor superfamily member 14 (LIGHT) expression with TLS signature genes, which are all markers for immune cell accumulation and better prognosis, through retrieving RNA sequencing (RNA-seq) data from patients with cancer, suggesting the potential of LIGHT in reconstituting a high immune-infiltrated tumor microenvironment. Accordingly, LIGHT co-expressed chimeric antigen receptor T (LIGHT CAR-T) cells not only showed enhanced cytotoxicity and cytokine production but also improved CCL19 and CCL21 expression by surrounding cells.

Correction: The interferon stimulated gene 20 protein (ISG20) is an innate defense antiviral factor that discriminates self versus non-self translation.

[This corrects the article DOI: 10.1371/journal.ppat.

Transcriptome analysis of a newly established mouse model of Toxoplasma gondii pneumonia.

Background: Toxoplasmosis is a zoonotic parasitic disease caused by Toxoplasma gondii. Toxoplasma gondii infection of the lungs can lead to severe pneumonia. However, few studies have reported Toxoplasma pneumonia.

UDP/P2Y contributes to enhancing LPS-induced acute lung injury by regulating neutrophil migration.

Neutrophils play a prominent role in the inflammatory response and are a critical factor in the pathogenesis of acute lung injury (ALI). Despite a deep understanding of neutrophil accumulation in the pulmonary microvasculature during the process of this disease, the regulatory mechanism of neutrophil recruitment remains unclear. This study aimed to explore the functions and signaling pathways of the purinergic receptor P2Y in mediating the innate immune response in ALI.

Inflammatory macrophages exacerbate neutrophil-driven joint damage through ADP/P2Y signaling in rheumatoid arthritis.

Rheumatoid arthritis (RA) is a chronic autoimmune disease that primarily affects the joints and is associated with excessive immune cell infiltration. However, the complex interactions between the immune cell populations in the RA synovium remain unknown. Here, we demonstrate that inflammatory macrophages in the synovium exacerbate neutrophil-driven joint damage in RA through ADP/P2Y signaling.

Blocking P2X7-Mediated Macrophage Polarization Overcomes Treatment Resistance in Lung Cancer.

P2X7, a crucial sensor of extracellular ATP, is widely distributed in different immune cells as a potent stimulant of inflammation and immunity. P2X7 is also highly expressed in immunosuppressive cells such as tumor-associated macrophages (TAM) and even tumor cells. However, the function and potential applications of P2X7-mediated immunosuppressive responses in the tumor microenvironment remain unclear.

Regulatory role of Gpr84 in the switch of alveolar macrophages from CD11b to CD11b status during lung injury process.

Acute respiratory distress syndrome (ARDS) is a kind of comprehensive disease with excessive inflammation and high clinical mortality. Multiple immune cells are involved in the ARDS process. Amongst these populations, lung-resident alveolar macrophages (AMs) are known to participate in the regulation of ARDS.

ADP/P2Y aggravates inflammatory bowel disease through ERK5-mediated NLRP3 inflammasome activation.

Inflammasomes are essential for inflammation and pathogen elimination in response to microbial infection and endogenous danger signals. However, the mechanism of inflammasome activation by endogenous danger signals mediated posttranslational modification and the connection between inflammasomes and inflammatory diseases remains elusive. In this study, we found that ADP was highly released from injured colonic tissue as a danger signal during inflammatory bowel disease.

Discovery of potent ureido tetrahydrocarbazole derivatives for cancer treatments through targeting tumor-associated macrophages.

Tumor-associated macrophages (TAMs) are one of the prominent components of the tumor microenvironment (TME). The polarization peculiarity of TAMs drives them to infiltrate and active with states between M1 (anti-tumor) and M2 (pro-tumor) phenotypes in cancers. Exploiting small molecular drugs through targeting TAMs to repolarize them into an antitumor phenotype is considered as a novel strategy for cancer treatments in recent years.

The interferon stimulated gene 20 protein (ISG20) is an innate defense antiviral factor that discriminates self versus non-self translation.

ISG20 is a broad spectrum antiviral protein thought to directly degrade viral RNA. However, this mechanism of inhibition remains controversial. Using the Vesicular Stomatitis Virus (VSV) as a model RNA virus, we show here that ISG20 interferes with viral replication by decreasing protein synthesis in the absence of RNA degradation.

Inhibition of Rspo-Lgr4 Facilitates Checkpoint Blockade Therapy by Switching Macrophage Polarization.

Therapies targeting immune checkpoints have shown great clinical potential in a subset of patients with cancer but may be hampered by a failure to reverse the immunosuppressive tumor microenvironment (TME). As the most abundant immune cells in TME, tumor-associated macrophages (TAM) play nonredundant roles in restricting antitumor immunity. The leucine-rich repeat-containing G-protein-coupled receptor 4 (Lgr4, also known as Gpr48) has been associated with multiple physiologic and pathologic functions.

Presenilin 2 deficiency facilitates Aβ-induced neuroinflammation and injury by upregulating P2X7 expression.

Accumulating evidence suggests that β-amyloid (Aβ)-induced neuroinflammation plays a prominent and early role in Alzheimer's disease (AD). In this study, we demonstrated that Presenilin 2 (PS2) deficiency facilitates Aβ-induced neuroinflammation and injury by upregulating P2X7 expression both in vitro and in vivo. PS2 knockout mice demonstrated increased cognitive impairments and cerebral injury.

Extracellular ADP facilitates monocyte recruitment in bacterial infection via ERK signaling.

As the most prominent clinical drug targets for the inhibition of platelet aggregation, P2Y and P2Y have been found to be highly expressed in both platelets and macrophages. However, the roles and function of P2Y in the regulation of macrophage-mediated innate immune responses remain unclear. Here, we demonstrate that adenosine 5'-diphosphate (ADP), the endogenous ligand of P2Y, P2Y and P2Y, was released both in E.

Long-term ketogenic diet contributes to glycemic control but promotes lipid accumulation and hepatic steatosis in type 2 diabetic mice.

The ketogenic diet (KD) has been widely used in weight and glycemic control, although potential side effects of long-term KD treatment have caused persistent concern. In this study, we hypothesized that the KD would ameliorate the progression of diabetes but lead to disruptions in lipid metabolism and hepatic steatosis in a mouse model of diabetes. In type 2 diabetic mouse model, mice were fed a high-fat diet and administered streptozotocin treatment before given the test diets for 8 weeks.

TLR-Activated Gap Junction Channels Protect Mice against Bacterial Infection through Extracellular UDP Release.

Extracellular UDP (eUDP), released as a danger signal by stressed or apoptotic cells, plays an important role in a series of physiological processes. Although the mechanism of eUDP release in apoptotic cells has been well defined, how the eUDP is released in innate immune responses remains unknown. In this study, we demonstrated that UDP was released in both Escherichia coli-infected mice and LPS- or Pam3CSK4-treated macrophages.