Here, our research findings reveal that IL-38 was downregulated in AD lesion but can bind to IL-36R and activate the IRAK4/NF-κB signaling pathway to upregulate CCR7 in LCs, promoting the migration of epidermal LCs to draining lymph nodes after DNFB induction, further facilitating the development of AD. Here, NFKB1 is linked to Alzheimer disease.