Multimodal analyses of vitiligo skin idenitfy tissue characteristics of stable disease

Year: 2022

Type: article

Abstract: Vitiligo is an autoimmune skin disease characterized by the destruction of melanocytes by autoreactive CD8+ T cells. Melanocyte destruction in active vitiligo is mediated by CD8+ T cells, but the persistence of white patches in stable disease is poorly understood. The interaction between immune cells, melanocytes, and keratinocytes in situ in human skin has been difficult to study due to the lack of proper tools. We combine noninvasive multiphoton microscopy (MPM) imaging and single-cell RNA-Seq (scRNA-Seq) to identify subpopulations of keratinocytes in stable vitiligo patients. We show that, compared with nonlesional skin, some keratinocyte subpopulations are enriched in lesional vitiligo skin and shift their energy utilization toward oxidative phosphorylation. Systematic investigation of cell-to-cell communication networks show that this small population of keratinocyte secrete CXCL9 and CXCL10 to potentially drive vitiligo persistence. Pseudotemporal dynamics analyses predict an alternative differentiation trajectory that generates this new population of keratinocytes in vitiligo skin. Further MPM imaging of patients undergoing punch grafting treatment showed that keratinocytes favoring oxidative phosphorylation persist in nonresponders but normalize in responders. In summary, we couple advanced imaging with transcriptomics and bioinformatics to discover cell-to-cell communication networks and keratinocyte cell states that can perpetuate inflammation and prevent repigmentation.

Source: JCI Insight

DOI: 10.1172/jci.insight.154585

Authors: Jessica Shiu, Lihua Zhang, Griffin Lentsch, Jessica L. Flesher, Suoqin Jin, Christopher Polleys, Seong Jin Jo, Craig Mizzoni, Pezhman Mobasher, Jasmine Kwan, Francisca Rius-Diaz, Bruce J. Tromberg, Irene Georgakoudi, Qing Nie, Mihaela Balu, Anand K. Ganesan

Institutions: University of California, Irvine, Beckman Laser Institute and Medical Clinic, Massachusetts General Hospital, Tufts University, Seoul National University, Universidad de Málaga

Language: English

Topic: melanin and skin pigmentation

Subfield: Cell Biology

Field: Biochemistry, Genetics and Molecular Biology

Domain: Life Sciences

SDG: Good health and well-being

Open Access status: gold

Estimated APC paid: $4,100

Funders: National Science Foundation, American Skin Association, Nihon University, National Institutes of Health, University of California, Irvine, National Cancer Institute, National Institute of Arthritis and Musculoskeletal and Skin Diseases, National Institute of Biomedical Imaging and Bioengineering, National Center for Research Resources, National Center for Advancing Translational Sciences

OpenAlex ID: W4281667756