Keratinocytes Function as Dynamic Immune Regulators and Gatekeepers of Skin Health

Keratinocytes (KCs), comprising over 90% of epidermal cells, are increasingly recognized beyond their structural role in forming the stratum corneum barrier. They are vital for immune surveillance, equipped with pattern recognition receptors like Toll-like and NOD-like receptors. This enables rapid detection of pathogen-associated molecular patterns (PAMPs) and damage-associated molecular patterns (DAMPs), initiating immune responses. Dysregulation in KC signaling is implicated in chronic inflammatory skin conditions such as psoriasis and atopic dermatitis, highlighting a critical gap in understanding their dual role in immune tolerance and inflammation.

This comprehensive review synthesized current literature on keratinocyte biology and immunology, examining their multifaceted roles in skin barrier function, immune surveillance, and inflammatory responses. Researchers analyzed studies detailing pattern recognition receptor signaling, cytokine and chemokine release, and antimicrobial peptide production by KCs. The review also explored how KCs support barrier stability through lipid and protein synthesis, and investigated the molecular pathways by which KCs respond to environmental stressors and microbial signals while maintaining epidermal integrity. The authors specifically focused on the link between abnormal KC signaling and various inflammatory skin conditions.

Keratinocytes dynamically regulate both innate and adaptive immune responses by expressing diverse pattern recognition receptors, including Toll-like and NOD-like receptors, which facilitate the immediate detection of PAMPs and DAMPs. This detection triggers the release of a broad spectrum of cytokines and chemokines, orchestrating immune cell recruitment and activation. KCs also contribute significantly to the skin's defense mechanisms by producing various antimicrobial peptides and by synthesizing essential lipids and proteins that maintain the integrity and stability of the stratum corneum barrier.

Abnormal signaling pathways within keratinocytes are directly linked to the pathogenesis of major inflammatory skin conditions, including psoriasis and atopic dermatitis, underscoring their pivotal role in immune tolerance and inflammation. The review emphasizes that KCs are not merely passive structural components but active participants in immune surveillance and regulation.