Keratinocytes: Dynamic Gatekeepers and Immune Regulators of the Skin

Keratinocytes (KCs) constitute more than 90% of epidermal cells and are increasingly recognized as key regulators of skin immunity. In addition to forming the stratum corneum barrier, KCs are essential for immune surveillance. They express various pattern recognition receptors, such as Toll-like and nucleotide-binding oligomerization domain (NOD)-like receptors, which enable the rapid detection of pathogen- and damage-associated molecular patterns. This detection then stimulates the release of cytokines and chemokines that regulate both innate and adaptive immune responses. In addition, KCs produce antimicrobial peptides and support barrier stability by synthesizing lipids and proteins. Abnormal signaling in KCs has been linked to inflammatory skin conditions, including psoriasis and atopic dermatitis. These findings highlight the dual role of KCs in regulating immune tolerance and inflammation. This review examines the molecular pathways by which KCs respond to environmental stressors and microbial signals while maintaining barrier integrity, highlighting their potential as therapeutic targets for skin diseases.