Granzyme B in epithelial barrier dysfunction and related skin diseases

The skin's barrier function is vital for defense and hydration. Stratum corneum proteins maintain this function. However, excessive proteolytic activity can disrupt barrier integrity. Granzyme B is a protease normally absent in healthy tissues but elevated during chronic inflammation. Its intracellular role in apoptosis is well known. Recent studies suggest extracellular roles in inflammation and tissue remodeling. Granzyme B may also cleave barrier proteins in the epidermis. This may lead to dysfunction in skin and other epithelia. Prior research has shown its involvement in immune responses and cytokine processing. No prior work had resolved its specific role in epithelial dysfunction.

This review aims to explore granzyme B's role in epidermal barrier dysfunction. It focuses on mechanisms and disease contexts. The authors seek to clarify how granzyme B affects barrier proteins. They also examine its contribution to immunoreactivity and tissue damage. The study addresses a gap in understanding protease-driven epithelial dysfunction. It aims to synthesize findings from recent literature. The goal is to highlight granzyme B's dual intracellular and extracellular roles. This review does not propose new hypotheses but compiles existing evidence.

The review approach includes synthesizing literature on granzyme B's proteolytic effects. It analyzes experimental and clinical studies on epithelial dysfunction. The authors use a narrative framework to organize findings. They categorize data by tissue type and disease context. They also assess mechanisms of granzyme B-mediated cleavage. Experimental inhibitors are reviewed for their utility in research and therapy. The synthesis is based on peer-reviewed articles published in recent years. The authors do not perform new experiments but compile and interpret existing data.

Granzyme B cleaves junctional proteins in the stratum corneum. This may lead to impaired epidermal barrier function. It also processes cytokines and matrix proteins in inflamed tissues. Experimental inhibitors have shown promise in reducing dysfunction. The enzyme contributes to dysfunction in airway, gut, and retinal epithelia. It may trigger immunoreactivity by exposing autoantigens. The review highlights specific diseases where granzyme B is implicated. These include atopic dermatitis and psoriasis.

The authors synthesize evidence that granzyme B promotes barrier dysfunction. They propose that cleavage of barrier proteins is a key mechanism. They note that this protease contributes to immunoreactivity and tissue remodeling. The review suggests that granzyme B may be a therapeutic target. However, the authors do not claim this as a definitive conclusion. They emphasize the need for further study on inhibitor efficacy. They also highlight the relevance of granzyme B in multiple epithelial contexts. The synthesis does not extend beyond the claims made in the literature reviewed.