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Light-sheet Microscopy for Three-dimensional Visualization of Human Immune Cells
Published on: June 13, 2018
3D deconvolution of human skin immune architecture with Multiplex Annotated Tissue Imaging System
Manon Scholaert1,2, Raissa Houmadi1, Jeremy Martin1
1Toulouse Institute for Infectious and Inflammatory Diseases (Infinity), INSERM UMR1291, CNRS UMR5051, and University Toulouse III, Toulouse, France.
Insights
A new system called MANTIS (Multiplex Annotated Tissue Imaging System) analyzes skin inflammation with high spatial resolution. It reveals common immune features in severe skin diseases and identifies disease-specific structures.
Area of Science:
- Dermatology
- Immunology
- Computational Pathology
Background:
- Conventional immunohistochemistry struggles to capture the complex immune cell distribution in skin diseases.
- Understanding regional immune heterogeneity is crucial for diagnosing and treating inflammatory skin conditions.
Purpose of the Study:
- To introduce MANTIS (Multiplex Annotated Tissue Imaging System), a novel analytical pipeline for spatially resolved immune phenotyping of skin tissues.
- To enable automated detection and quantification of immune cells and biomarkers within complex inflammatory skin lesions.
Main Methods:
- Development of MANTIS, a flexible pipeline compatible with routine clinical practice.
- Utilizing phenotype attribution matrices and α-shape algorithms for digital immune landscape projection.
- Automated detection of inflammatory clusters and single-cell biomarker quantification.
Main Results:
- MANTIS successfully projects digital immune landscapes and quantifies biomarkers in skin samples.
- Severe lesions in systemic lupus erythematosus, Kawasaki syndrome, and COVID-19-associated skin issues share common immune features.
- Nonrandom cell distribution and disease-specific dermal immune structures were identified.
Conclusions:
- MANTIS offers accurate and flexible spatial immune phenotyping for skin manifestations.
- The system aids in understanding the spatial organization of immune environments in skin diseases.
- MANTIS facilitates a deeper comprehension of the pathophysiology of various skin conditions.
Abstract:
Routine clinical assays, such as conventional immunohistochemistry, often fail to resolve the regional heterogeneity of complex inflammatory skin conditions. We introduce MANTIS (Multiplex Annotated Tissue Imaging System), a flexible analytic pipeline compatible with routine practice, specifically designed for spatially resolved immune phenotyping of the skin in experimental or clinical samples. On the basis of phenotype attribution matrices coupled to α-shape algorithms, MANTIS projects a representative digital immune landscape while enabling automated detection of major inflammatory clusters and concomitant single-cell data quantification of biomarkers. We observed that severe pathological lesions from systemic lupus erythematosus, Kawasaki syndrome, or COVID-19-associated skin manifestations share common quantitative immune features while displaying a nonrandom distribution of cells with the formation of disease-specific dermal immune structures. Given its accuracy and flexibility, MANTIS is designed to solve the spatial organization of complex immune environments to better apprehend the pathophysiology of skin manifestations.

