TNFSF14 inhibits melanogenesis via NF-kB signaling in melanocytes

Abstract Melanin synthesisin melanocytesis affected by various cytokines. Here, we reported for the first time that tumor necrosis factor superfamily member 14 (TNFSF14) inhibits melanogenesis in the primary culture of human epidermal melanocytes. TNFSF14 is known to bind to its receptors herpes virus entry mediator (HVEM) and lymphotoxinβ receptor (LTβR) for signal transduction, but TNFSF14-induced hypopigmentationwas independent of HVEM and LTβR in melanocytes. To explore signaling in melanocytestreated with TNFSF14, we performed RNA-seqand found that nuclear factor κ-light-chain-enhancer of activated B cells (NF-κB) signaling is activated by TNFSF14. Further, we observed that inhibition of NF-kB effectively blocks the hypopigmentationinduced by TNFSF14. We conclude that TNFSF14 inhibits melanogenesis in melanocytesvia NF-κB signaling and could be applied in the treatment of cutaneous pigment disorders.