Single-cell transcriptomics combined with interstitial fluid proteomics defines cell type–specific immune regulation in atopic dermatitis - 04/11/20
Abstract |
Background |
Atopic dermatitis (AD) is the most common chronic inflammatory skin disease, but its complex pathogenesis is only insufficiently understood, resulting in still limited treatment options.
Objective |
We sought to characterize AD on both transcriptomic and proteomic levels in humans.
Methods |
We used skin suction blistering, a painless and nonscarring procedure that can simultaneously sample skin cells and interstitial fluid. We then compared results with conventional biopsies.
Results |
Suction blistering captured epidermal and most immune cells equally well as biopsies, except for mast cells and nonmigratory CD163+ macrophages that were only present in biopsy isolates. Using single-cell RNA sequencing, we found comparable transcriptional profiles of key inflammatory pathways between blister and biopsy AD, but suction blistering was superior in cell-specific resolution for high-abundance transcripts (KRT1/KRT10, KRT16/KRT6A, S100A8/S100A9), which showed some background signals in biopsy isolates. Compared with healthy controls, we found characteristic upregulation of AD-typical cytokines such as IL13 and IL22 in Th2 and Th22 cells, respectively, but we also discovered these mediators in proliferating T cells and natural killer T cells, that also expressed the antimicrobial cytokine IL26. Overall, not T cells, but myeloid cells were most strongly enriched in AD, and we found dendritic cell (CLEC7A, amphiregulin/AREG, EREG) and macrophage products (CCL13) among the top upregulated proteins in AD blister fluid proteomic analyses.
Conclusion |
These data show that by using cutting-edge technology, suction blistering offers several advantages over conventional biopsies, including better transcriptomic resolution of skin cells, combined with proteomic information from interstitial fluid, unraveling novel inflammatory players that shape the cellular and proteomic microenvironment of AD.
Le texte complet de cet article est disponible en PDF.Key words : single-cell RNA sequencing, Olink proteomics, atopic dermatitis, suction blistering
Abbreviations used : AD, C0, DC, DC-1, FACS, HC, ILC, KC, KC-0, NK, pDC, scRNA-seq, TCELL-1, TREG, UMAP
Plan
| This work was funded by a research grant to P.M.B. from the LEO Foundation, Copenhagen, Denmark. V.V. is supported by the Vienna Business Agency (Vienna, Austria; grant “APOSEC to clinic” 2343727), and the Aposcience AG. T.K. is supported by a Lise-Meitner fellowship from the Austrian Science Fund (FWF M2403). A.E.B. is supported by the FWF (P31485-B30 and DK-W1248-B30). C. Bock is supported by a New Frontiers Group award of the Austrian Academy of Sciences and by an ERC Starting Grant (European Union’s Horizon 2020 research and innovation program, grant agreement no. 679146). |
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| Disclosure of potential conflict of interest: P.M.B. is an employee of the Medical University of Vienna; has received personal fees from LEO Pharma, Pfizer, Sanofi, Eli Lilly, Novartis, Celgene, UCB Pharma, Biotest, Boehringer Ingelheim, AbbVie, and Arena Pharmaceuticals; and is an investigator for Novartis (grants paid to his institution). The rest of the authors declare that they have no relevant conflicts of interest. |
Vol 146 - N° 5
P. 1056-1069 - novembre 2020 Retour au numéro
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