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HDAC3 inhibition stabilizes the IL-37 receptor module to enhance anti-inflammatory signaling in cystic fibrosis airway epithelium

Airway inflammation in cystic fibrosis (CF) persists despite advances in CFTR modulator therapy. IL-37b suppresses innate immune signaling through a receptor complex containing IL-18R and wild-type SIGIRR (WT-SIGIRR; IL-1R8), but this pathway is compromised in CF airway epithelial cells by the dominant-negative exon 8-skipped SIGIRR isoform ({Delta}8-SIGIRR). Here, a natural-product screen identified short-chain fatty acids as preferential enhancers of WT-SIGIRR.

bioRxiv 5d ago

p38 dependent IL-33 responses define a conserved inflammatory programme in mast cells

Interleukin-33 (IL-33) is a key cytokine in mast cell mediated immunity, promoting inflammatory cytokine production without inducing degranulation. Here, we compared IL-33 induced proteomic responses across three mast cell culture systems, Foetal Liver derived Mast Cells (FLMCs), Bone Marrow derived Mast Cells (BMMCs), and Peritoneal Mast Cells (PMCs), using quantitative data-independent acquisition mass spectrometry. Although baseline proteomes were largely conserved across all mast cell...

bioRxiv 9d ago

Mize lands on IL, further depleting Tigers' rotati...

The Tigers placed starter Casey Mize on the IL with right adductor inflammation on Friday.

ESPN 11d ago

Clinical isolates of Mycobacterium avium complex reveal an M. intracellulare-associated IL-17/neutrophilic pulmonary immune program in a murine disease model

Mycobacterium avium complex (MAC) is the leading cause of nontuberculous mycobacterial pulmonary disease (NTM-PD) and mainly comprises M. avium (MAV) and M. intracellulare (MI). Host-pathogen interactions may contribute to the heterogeneous clinical course of MAC pulmonary disease (MAC-PD); however, species- or isolate-associated differences in virulence and host immune responses induced by MAC strains remain poorly understood. Here, we established a panel of MAC clinical isolates exhibiting...

bioRxiv 10d ago

Chibil: A C compiler targeting .NET IL

Chibil is a C compiler based on chibicc rewritten in C# and updated to target .NET It is complete enough to run DOOM (PureDOOM). Chibil takes C source files and generates COFF OBJ files.

Hacker News 9d ago

Redundant γc cytokines license IL-1-driven neutrophil inflammation through MEK/ERK convergence

Interleukin 1 (IL1) is a central driver of autoinflammatory disease, yet IL1 blockade often provides incomplete benefit in complex, neutrophil-driven conditions. Here we identify a licensing circuit in which common gamma chain cytokines provide a redundant signal required for maximal IL1 driven neutrophil inflammation. IL1 and gamma chain cytokines synergize to drive inflammatory cytokine production exceeding either stimulus alone, and these signals engage the MEK/ERK pathway, an effect...

bioRxiv 9d ago

Yankees catcher Wells joins Stanton, Judge on IL

For the second time in less than 24 hours, the Yankees made an unexpected move with their catching group Saturday night when Austin Wells was placed on the injured list with cervical headaches before the team took the field against the Boston Red Sox. J.C. Escarra was recalled from Triple-A Scranton/Wilkes-Barre to replace Wells on the roster. The Yankees had optioned Escarra late Friday, choosing to swap him out for Ali Sánchez.

ESPN 3d ago

QBE – Compiler Back end: Version 1.3

QBE 1.3 took a while to cook, but it is the most significant release since 1.0 with around 7k new lines of code and 1.5k deleted ones. In addition to the usual bug fixes, QBE gained a new and original IL matching algorithm, new optimizations from Roland Paterson-Jones, Scott Graham added support for the Windows ABI, and I implemented a plan suggested by Michael Forney to have QBE produce position-independent code (as in shared objects). QBE is teamwork, and I am happy to thank all the...

Hacker News 7d ago