Yuanqiang Sun, Wenchao Li, Zhenzhen Wang, Yongliang Yang, Ziyang Zhang, Gongqi Yu, Chuan Wang, Xu Sang, Yingjie Lin, Guangliang Zhang, Haixia Wang, Yilei Wu, Jianwen Wang, Fuxiang Bai, Jianju Liu, Hong Liu, Furen Zhang
This study elucidates the dynamic remodeling of immunometabolism centered on macrophages during P. verrucosa infection, and demonstrates that the CCL2/CCR2 biological axis contributes to host antifungal immunity mainly by modulating immune cell recruitment and the balance of inflammatory phenotypes. These findings provide a novel theoretical basis for understanding the immunoregulatory mechanisms of dematiaceous fungal infections and developing potential immunological intervention strategies.
Understanding how genetic variation shapes tissue-specific protein expression is fundamental for uncovering disease mechanisms and therapeutic targets. However, the proteomic landscape and its underlying genetic regulation in skin, the largest human organ, remain largely uncharted. Here, we present a population-level skin proteomic dataset, quantifying 5,774 proteins across 248 individuals and revealing substantial inter-individual variation shaped by genetic and non-genetic factors. Genome-wide pQTL analysis identifies 1,765 significant variant-protein associations involving 36 proteins, with 62% unsupported by skin eQTL and 33% not replicated in non-skin pQTL. Integrating skin pQTL with ancestry-matched leprosy GWAS identifies 11 risk proteins through proteome-wide association study (PWAS), with four showing causal evidence from colocalization or Mendelian randomization analyses. Further integration with European GWASs for atopic dermatitis and psoriasis identifies known and novel disease-related proteins, demonstrating the cross-ancestry utility of skin pQTL. Together, this work establishes a valuable resource for skin proteogenomics and disease-gene discovery in dermatology.