Keratinocyte antimicrobial peptide expression pathways

Keratinocyte antimicrobial peptide (AMP) expression pathways are essential components of the skin's innate immune system, responsible for the production of effector molecules like cathelicidins (LL-37) and defensins (hBDs). These pathways are activated by various stimuli, including microbial patterns recognized by Toll-like receptors (TLRs), metabolic signals through the Vitamin D receptor (VDR), and pro-inflammatory cytokines such as IL-17 and IL-22 acting via the JAK/STAT3 signaling axis. In healthy skin, these pathways maintain microbial homeostasis and facilitate wound healing by promoting cell migration and angiogenesis. However, dysregulation is central to several dermatological conditions: psoriasis is characterized by an overactive AMP response that fuels a pro-inflammatory loop, while atopic dermatitis often involves a deficiency in AMPs, predisposing patients to infections. Therapeutic strategies involve either inducing these pathways (e.g., using Vitamin D analogs for wound healing or infections) or inhibiting them (e.g., using JAK inhibitors or IL-17 blockers for psoriasis) to restore skin homeostasis. The modulation of these pathways is a key focus in developing treatments for chronic inflammatory skin diseases and impaired wound healing. For instance, synthetic AMPs are being explored as novel anti-infective agents to overcome antibiotic resistance. Additionally, targeting the upstream regulators of these pathways, such as the IL-23/IL-17 axis, has revolutionized the management of moderate-to-severe psoriasis.

Other names

Keratinocyte AMP expressionEpidermal antimicrobial responseInnate immune pathways in keratinocytesAMP induction pathways

Modulation of innate immune signaling through Vitamin D receptor (VDR) agonism, JAK/STAT inhibition, and neutralization of IL-17/IL-23 cytokines to regulate the production of antimicrobial peptides.