Comparative single-cell transcriptome analysis reveals ethnicity-specific immune activation in psoriasis.

Summary: Abstract Body: Psoriasis (PSO) is a chronic inflammatory disease with varying clinical presentations and severity among populations. While large plaque psoriasis is more common in Caucasians, Asians typically present with small plaques despite increased levels of IL-17-related inflammatory cytokines. We performed single-cell transcriptomics analysis on skin biopsy samples from Korean PSO patients to comparative analyze the Caucasian PSO and healthy controls (HC). We analyzed a total of 281,731 cells and identified TNC+IL1R1+ fibroblasts and CCR7+LAMP3- Myeloid cells, both of which were significantly increased in PSO lesion compared to HC. TNC+IL1R1+ fibroblasts which exhibit activation of the TNF pathway and contribute to type 3 inflammation. By expression of CCL2 and CCL19, TNC+IL1R1+ Fibroblasts also promote the migration of myeloid cells, which contribute to keratinocyte proliferation and activation adaptive immune response. Among these myeloid cells, CCR7+LAMP3- myeloid cells were significantly enriched in Caucasian lesions compared to HC and Asian lesions. These cells expressed IL23A and CCL20 contributing to the radial expansion of psoriasis. We suggest that the progression of psoriasis is driven by specific fibroblasts and myeloid cells, which together amplify inflammation and tissue remodeling. These findings highlight the need for ethnicity-specific therapeutic strategies in psoriasis management. Hyun Seung Choi¹, Christine Suh-Yun Joh¹, Hyo Jeong Nam¹, Soyoung Jeong¹, Hyun Woo Kim¹, Jeong Eun Kim^{2, 3}, Hyun Je Kim^{1, 6, 7}, Tae-Gyun Kim^{4, 5} 1. Department of Biomedical Sciences, Seoul National University Graduate School, Seoul, Korea (the Republic of). 2. Department of Dermatology, Hanyang University, Seongdong-gu, Seoul, Korea (the Republic of). 3. Hanyang institute of Bioscience and Biotechnology, Hanyang University, Seongdong-gu, Seoul, Korea (the Republic of). 4. Department of Dermatology, Severance Hospital, Cutaneous Biology Research Institute, Yonsei University, Seodaemun-gu, Seoul, Korea (the Republic of). 5. Institute for Immunology and Immunological Diseases, Yonsei University College of Medicine, Seodaemun-gu, Seoul, Korea (the Republic of). 6. Department of Dermatology, Seoul National University Hospital, Jongno-gu, Seoul, Korea (the Republic of). 7. Cancer Research Institute, Seoul National University College of Medicine, Jongno-gu, Seoul, Korea (the Republic of). Bioinformatics, Computational Biology, and Imaging