Immune Microenvironment Remodeling in Digestive Diseases: Molecular Mechanisms and Bioengineered Therapeutic Strategies

Digestive diseases encompass a broad spectrum of gastrointestinal, hepatobiliary, and pancreatic disorders that are increasingly understood as immune microenvironment-driven conditions. Their initiation and progression are governed by complex cellular and molecular interactions involving epithelial, endothelial, stromal, and immune cells, as well as the microbiome. Recent breakthroughs in single-cell and spatial omics, proteomics, metabolomics, and advanced molecular imaging have revealed new layers of immune regulation, heterogeneity, and spatial niche organization in these diseases. These techniques have uncovered previously unrecognized immune subsets, immune–fibrotic crosstalk dynamics, metabolic reprogramming, and disease-stage–specific signatures. Despite these advances, translation of mechanistic understanding into effective immune-targeted diagnostics and therapies remains incomplete, largely due to limited integration of immune biology with engineering-driven intervention strategies. This gap highlights the need for comprehensive studies bridging immune remodeling mechanisms with bioengineered therapeutic innovation.

This Research Topic aims to advance understanding of how immune microenvironments are remodeled in digestive diseases and how these processes can be therapeutically reprogrammed. The goal is to highlight studies that explore molecular and cellular mechanisms of immune modulation, immune–stromal interactions, metabolic regulation, and immune-fibrotic signaling, as well as to promote translational research developing bioengineered or nano-enabled therapeutics for immune microenvironment modulation. We seek contributions that provide mechanistic, technological, or preclinical insight into the pathogenesis and treatment of inflammatory, fibrotic, metabolic, and malignant digestive diseases. Through a focus on mechanistic depth and translational innovation, this Research Topic aims to foster a systematic framework for immune-based diagnosis and therapy.

To gather further insights into immune microenvironment remodeling in digestive diseases, we welcome contributions within the boundaries of molecular immunology, spatial omics, and bioengineering approaches. Submissions may address, but are not limited to, the following themes:

• Cellular and molecular mechanisms of innate and adaptive immune activation, tolerance, and exhaustion
• Immune–fibrotic and immune–metabolic crosstalk in inflammation, fibrosis, and carcinoma progression
• Spatial and multi-omics mapping of immune landscapes in digestive tissues
• Barrier immunity, gut-liver axis communication, and immune-driven regeneration
• Computational modeling and system-level integration of immune remodeling
• Bioengineered and nanotechnology-based therapeutic strategies, including lipid nanoparticles, extracellular vesicles, hydrogel systems, and CRISPR delivery platforms
• Safety, biodistribution, immunogenicity, and translational feasibility of engineered immunotherapies

Article types: Original Research, Review, Mini Review, Perspective, Methods, Brief Research Report