Chronic Rhinosinusitis with Nasal Polyps: A "Module-First" Review of Murine Models and Chemical Interventions

Area of Science:

• Immunology
• Pathology
• Translational Medicine

Background:

• Chronic rhinosinusitis with nasal polyps (CRSwNP) has diverse molecular subtypes not fully matching clinical presentations, hindering targeted treatments.
• Current human studies identify pathways but lack in vivo systems for causal links to disease mechanisms.
• Developing perturbable in vivo models is crucial for attributing specific molecular nodes to CRSwNP lesion formation and tissue remodeling.

Purpose of the Study:

• To present a "module-first" framework connecting murine models to epithelial-immune-stromal circuits for CRSwNP research.
• To establish a minimal, module-matched endpoint set for reproducible causal inference in CRSwNP pathogenesis.
• To propose a standardized roadmap for accelerating mechanism-linked discovery and preclinical validation of drug targets in CRSwNP.

Main Methods:

• Summarized common CRSwNP-like induction protocols in murine models (e.g., allergen, protease, SEB, innate triggers).
• Defined operational pathology terms like "polyp-like lesion" vs. "true polyp" for clarity.
• Proposed a causal template for key pathway modules (e.g., alarmins/IL-33-NF-κB, type 2/ILC2-eosinophil, IL-17A/neutrophil, Wnt/EMT, JAK/STAT).

Main Results:

• Organized chemical and molecular interventions based on their leverage points within the proposed pathway modules.
• Recommended an ARRIVE-aligned Minimum Reporting Set to standardize model anchoring and target engagement.
• Highlighted the dynamic and overlapping nature of pathway modules in vivo.

Conclusions:

• The module-first framework provides a heuristic for organizing CRSwNP research and standardizing preclinical validation.
• This approach aims to accelerate the identification and validation of tractable drug targets for CRSwNP.
• Improved standardization and causal inference are key to advancing CRSwNP treatment strategies.