JT002, a small molecule inhibitor of the NLRP3 inflammasome for the treatment of autoinflammatory disorders.

The NLRP3 inflammasome is an intracellular, multiprotein complex that promotes the auto-catalytic activation of caspase-1 and the subsequent maturation and secretion of the pro-inflammatory cytokines, IL-1β and IL-18. Persistent activation of the NLRP3 inflammasome has been implicated in the pathophysiology of a number of inflammatory and autoimmune diseases, including neuroinflammation, cardiovascular disease, non-alcoholic steatohepatitis, lupus nephritis and severe asthma. Here we describe the preclinical profile of JT002, a novel small molecule inhibitor of the NLRP3 inflammasome.

Therapeutic benefits of recombinant alpha1-antitrypsin IgG1 Fc-fusion protein in experimental emphysema.

Background: Alpha-1 antitrypsin (AAT) is a major serine protease inhibitor. AAT deficiency (AATD) is a genetic disorder characterized by early-onset severe emphysema. In well-selected AATD patients, therapy with plasma-derived AAT (pAAT), "augmentation therapy", provides modest clinical improvement but is perceived as cumbersome with weekly intravenous infusions.

Plasticity of Naturally Occurring Regulatory T Cells in Allergic Airway Disease Is Modulated by the Transcriptional Activity of .

The impact of naturally occurring regulatory T cells (nTregs) on the suppression or induction of lung allergic responses in mice depends on the nuclear environment and the production of the pro-inflammatory cytokine interleukin 6 (IL-6). These activities were shown to be different in nTregs derived from wild-type (WT) and CD8-deficient mice (CD8), with increased IL-6 levels in nTregs from CD8 mice in comparison to WT nTregs. Thus, identification of the molecular mechanisms regulating IL-6 production is critical to understanding the phenotypic plasticity of nTregs.

Dichotomous role of TGF-β controls inducible regulatory T-cell fate in allergic airway disease through Smad3 and TGF-β-activated kinase 1.

Background: Inducible CD4CD25 regulatory T (iTreg) cells can become pathogenic effector cells, enhancing lung allergic responses.

Objective: We aimed to define the underlying cellular and molecular pathways activated by TGF-β, which determine the suppressor or enhancing activities of iTreg cells.

Methods: Sensitized wild-type and CD8-deficient (CD8) mice were challenged with allergen.