cGAS-STING DNA-sensing in inflammatory bowel diseases.

Inflammatory bowel diseases (IBD) are chronic, incurable pathologies with unknown causes, affecting millions of people. Pediatric-onset IBD, starting before the age of 18 years, are increasing, with more aggressive and extensive features than adult-onset IBD. These differences remain largely unexplained.

Lack of FMRP in the retina: Evidence of a retinal specific transcriptomic profile.

Fragile X Syndrome (FXS), the most common inherited form of human intellectual disability, is a monogenic neurodevelopmental disorder caused by a loss-of-function mutation of the FMR1 gene. FMR1 is encoding the Fragile X Messenger Ribonucleo Protein (FMRP) an RNA-binding protein that regulates the translation of synaptic proteins. The absence of FMRP expression has many important consequences on synaptic plasticity and function, leading to the FXS clinical phenotype.

Interactions between the omnivorous bug Nesidiocoris tenuis (Heteroptera: Miridae) and the tomato pests Helicoverpa armigera (Lepidoptera: Noctuidae) and Phthorimaea absoluta (Lepidoptera: Gelechiidae): predation, phytophagy, and prey preference.

Nesidiocoris tenuis (Reuter) (Heteroptera: Miridae) is a zoophytophagous bug that can derive nutrients from 3 trophic levels: plants, herbivorous arthropods, and other predators. On tomato, besides damaging the plants as they feed, might the mirid also forage on pest species and repel pests. In greenhouse and laboratory experiments, we investigated the functional response of the bug, its prey preference, and its influence on the oviposition potentials of 2 major pest species Helicoverpa armigera (Hübner) (Lepidoptera: Noctuidae) and Phthorimaea absoluta Meyrick (Lepidoptera: Gelechiidae) on tomato Solanum lycopersicum L.

NLRP6 negatively regulates type 2 immune responses in mice.

Background: Inflammasomes are large protein complexes that assemble in the cytosol in response to danger such as tissue damage or infection. Following activation, inflammasomes trigger cell death and the release of biologically active forms of pro-inflammatory cytokines interleukin (IL)-1β and IL-18. NOD-like receptor family pyrin domain containing 6 (NLRP6) inflammasome is required for IL-18 secretion by intestinal epithelial cells, macrophages, and T cells, contributing to homeostasis and self-defense against pathogenic microbes.

STING agonist diABZI induces PANoptosis and DNA mediated acute respiratory distress syndrome (ARDS).

Stimulator of interferon genes (STING) contributes to immune responses against tumors and may control viral infection including SARS-CoV-2 infection. However, activation of the STING pathway by airway silica or smoke exposure leads to cell death, self-dsDNA release, and STING/type I IFN dependent acute lung inflammation/ARDS. The inflammatory response induced by a synthetic non-nucleotide-based diABZI STING agonist, in comparison to the natural cyclic dinucleotide cGAMP, is unknown.

The Micro-Immunotherapy Medicine 2LEID Exhibits an Immunostimulant Effect by Boosting Both Innate and Adaptive Immune Responses.

This study aimed at evaluating the effects of the micro-immunotherapy medicine (MIM) 2LEID, both in vitro and in vivo, on several components of the innate and adaptive immune system. MIM increased the phagocytic activity of macrophages, and it augmented the expression of the activation markers CD69 and HLA-DR in NK cells and monocytes/macrophages, respectively. The effect of MIM was evaluated in a model of respiratory infection induced by virus administration to immunocompetent mice in which it was able to improve neutrophil recruitment within the lungs ( = 0.

The Dual Targeting of FcRn and FcγRs Monomeric Fc Fragments Results in Strong Inhibition of IgG-Dependent Autoimmune Pathologies.

Novel molecules that directly target the neonatal Fc receptor (FcRn) and/or Fc gamma receptors (FcγRs) are emerging as promising treatments for immunoglobulin G (IgG)-dependent autoimmune pathologies. Mutated Fc regions and monoclonal antibodies that target FcRn are currently in clinical development and hold promise for reducing the levels of circulating IgG. Additionally, engineered structures containing multimeric Fc regions allow the dual targeting of FcRn and FcγRs; however, their tolerance needs to first be validated in phase I clinical studies.

Bromodomain and extraterminal (BET) protein inhibition of IgG/IgE production in murine B cells is counter-balanced by a strong Th2 bias.

Objectives: Inhibitors of bromodomain and extra terminal domain (BET) proteins are a new and growing class of anti-cancer drugs, which decrease oncogene expression by targeting superenhancers. Antibody production is another physiological process relying on superenhancers, and it remains to be clarified whether potential immunomodulatory properties of BET inhibitors might impact humoral immunity and allergy.

Methods: We thus evaluated humoral immune responses and their Th2 context and in mice following treatment with the classical BET-inhibitor JQ1.

Aryl hydrocarbon receptor (Ahr)-dependent Il-22 expression by type 3 innate lymphoid cells control of acute joint inflammation.

The aryl hydrocarbon receptor (AHR) controls several inflammatory and metabolic pathways involved in various diseases, including the development of arthritis. Here, we investigated the role of AHR activation in IL-22-dependent acute arthritis using the K/BxN serum transfer model. We observed an overall reduction of cytokine expression in Ahr-deficient mice, along with decreased signs of joint inflammation.

Oxidative Stress in Ozone-Induced Chronic Lung Inflammation and Emphysema: A Facet of Chronic Obstructive Pulmonary Disease.

Oxidative stress plays an important role in the pathogenesis of chronic obstructive pulmonary disease (COPD) caused by cigarette smoke and characterized by chronic inflammation, alveolar destruction (emphysema) and bronchiolar obstruction. Ozone is a gaseous constituent of urban air pollution resulting from photochemical interaction of air pollutants such as nitrogen oxide and organic compounds. While acute exposure to ozone induces airway hyperreactivity and neutrophilic inflammation, chronic ozone exposure in mice causes activation of oxidative pathways resulting in cell death and a chronic bronchial inflammation with emphysema, mimicking cigarette smoke-induced COPD.

Hippocampal interleukin-33 mediates neuroinflammation-induced cognitive impairments.

Background: Interleukin (IL)-33 is expressed in a healthy brain and plays a pivotal role in several neuropathologies, as protective or contributing to the development of cerebral diseases associated with cognitive impairments. However, the role of IL-33 in the brain is poorly understood, raising the question of its involvement in immunoregulatory mechanisms.

Methods: We administered recombinant IL-33 (rmIL-33) by intra-hippocampal injection to C57BL/6 J (WT) and IL-1αβ deficient mice.

Effects of Nintedanib in an Animal Model of Liver Fibrosis.

Systemic sclerosis can affect multiple internal organs, including the liver and lungs. Nintedanib, an antifibrotic approved for treatment of interstitial lung disease associated with systemic sclerosis, may have activity outside of the lungs. This study explored the effect of preventive and therapeutic nintedanib treatment in a 3-week carbon tetrachloride (CCL)-induced (500 mg/kg/day twice weekly for 3 weeks) model of hepatic inflammation and fibrosis in C57Bl/6 mice (aged 8 weeks, = 5 per group).

Potential Role of the Micro-Immunotherapy Medicine 2LALERG in the Treatment of Pollen-Induced Allergic Inflammation.

In this study, we evaluated the efficacy of a micro-immunotherapy medicine (MIM), 2LALERG, in a preclinical model of allergic respiratory disease sensitized with birch pollen extract (BPE). BALB/c mice were immunized with BPE, or saline solution, and were then challenged. Micro-immunotherapy medicine pillules were diluted in water, and 3 doses (0.

Ozone-Induced Aryl Hydrocarbon Receptor Activation Controls Lung Inflammation via Interleukin-22 Modulation.

Airborne ozone exposure causes severe lung injury and inflammation. The aryl hydrocarbon Receptor (AhR) (1), activated in pollutant-induced inflammation, is critical for cytokine production, especially IL-22 and IL-17A. The role of AhR in ozone-induced lung inflammation is unknown.

The alternative cap-binding complex is required for antiviral defense in vivo.

Cellular response to environmental challenges requires immediate and precise regulation of transcriptional programs. During viral infections, this includes the expression of antiviral genes that are essential to combat the pathogen. Transcribed mRNAs are bound and escorted to the cytoplasm by the cap-binding complex (CBC).

Acute Respiratory Barrier Disruption by Ozone Exposure in Mice.

Ozone exposure causes irritation, airway hyperreactivity (AHR), inflammation of the airways, and destruction of alveoli (emphysema), the gas exchange area of the lung in human and mice. This review focuses on the acute disruption of the respiratory epithelial barrier in mice. A single high dose ozone exposure (1 ppm for 1 h) causes first a break of the bronchiolar epithelium within 2 h with leak of serum proteins in the broncho-alveolar space, disruption of epithelial tight junctions and cell death, which is followed at 6 h by ROS activation, AHR, myeloid cell recruitment, and remodeling.

Self-DNA Sensing in Lung Inflammatory Diseases.

Self-DNA sensing by the immune system has emerged as a key contributing response in the pathogenesis of cancer and autoimmune diseases. Recent studies have established that release of nuclear and mitochondrial DNA can also drive lung inflammatory diseases. Here, we review the latest advances on self-DNA sensing and signaling, the influence of these pathways on lung inflammation, and how these findings contribute to our understanding of basic mechanisms of innate immunity.

Sterile Lung Inflammation Induced by Silica Exacerbates Mycobacterium tuberculosis Infection via STING-Dependent Type 2 Immunity.

Lung inflammation induced by silica impairs host control of tuberculosis, yet the underlying mechanism remains unclear. Here, we show that silica-driven exacerbation of M. tuberculosis infection associates with raised type 2 immunity.

STING-dependent sensing of self-DNA drives silica-induced lung inflammation.

Silica particles induce lung inflammation and fibrosis. Here we show that stimulator of interferon genes (STING) is essential for silica-induced lung inflammation. In mice, silica induces lung cell death and self-dsDNA release in the bronchoalveolar space that activates STING pathway.