Identification of an activated langerhans cell population and its role in cutaneous immunity

Summary: Langerhans cells (LCs) are a specialized subset of epidermal antigen-presenting cells that form a dense network essential for wound healing and immune homeostasis in both mice and humans. However, what attracts LCs to wounded areas remains unclear and whether a distinct LCs population exists in the injured epidermis, separate from steady-state and migratory stages. In this study, we utilized transgenic mice, intravital imaging, single-cell mRNA sequencing, and advanced data analysis techniques to characterize distinct stages of LCs activation. To induce local inflammation, we applied both physical and chemical skin treatments, and at the transcriptional level, LCs exhibited a similar response to both stimuli. We identified a previously unrecognized activated LCs stage through data integration, characterized by specific surface markers, which we validated using FACS analysis. A key feature of this activated stage was the upregulation of various complement system components and their receptors. Using C3 knockout mice, we observed reduced LCs accumulation at the edges of wounds, suggesting that C3 plays a critical role in recruiting activated LCs to the wound site. Furthermore, inducing LCs activation with ovalbumin led to enhanced early CD4+ T cell activation in draining lymph nodes and an increased B cell response, supported by elevated levels of anti-OVA IgG antibodies. These findings provide deeper insight into LC-mediated immune responses and wound healing mechanisms. Additionally, they may contribute to the development of novel non-invasive vaccines that leverage LCs activation for enhanced antigen uptake and immune priming. Artem Kiselev^{1, 3}, Axel Schmitter^{1, 3}, Sudhanshu Mishra^{1, 3}, Gun Woo Lee^{1, 3}, Sangbum Park^{1, 3, 2} 1. Institute for Quantitative Health Science and Engineering (IQ), Michigan State University, East Lansing, MI, United States. 2. Division of Dermatology, Department of Medicine, College of Human Medicine,, Michigan State University, East Lansing, MI, United States. 3. Department of Pharmacology and Toxicology, College of Human Medicine, Michigan State University, East Lansing, MI, United States. Epidermal Structure and Barrier Function