Characterization of Vascular Niche in Systemic Sclerosis by Spatial Proteomics.

Autor:	Rius Rigau A; Department of Internal Medicine 3, Rheumatology and Clinical Immunology (A.R.R., G.S., J.H.W.D., M.L.), Friedrich-Alexander-University Erlangen-Nürnberg and University Hospital Erlangen, Germany.; Deutsches Zentrum Immuntherapie (A.R.R., G.S., J.H.W.D., M.L.), Friedrich-Alexander-University Erlangen-Nürnberg and University Hospital Erlangen, Germany., Li YN; Clinic for Rheumatology (Y.-N.L., A.-E.M., A.-H.G., V.D., A.G., J.H.W.D., M.L.), University Hospital Düsseldorf, Medical Faculty of Heinrich Heine University, Germany.; Hiller Research Center (Y.-N.L., A.-E.M., A.-H.G., V.D., A.G., J.H.W.D., M.L.), University Hospital Düsseldorf, Medical Faculty of Heinrich Heine University, Germany., Matei AE; Clinic for Rheumatology (Y.-N.L., A.-E.M., A.-H.G., V.D., A.G., J.H.W.D., M.L.), University Hospital Düsseldorf, Medical Faculty of Heinrich Heine University, Germany.; Hiller Research Center (Y.-N.L., A.-E.M., A.-H.G., V.D., A.G., J.H.W.D., M.L.), University Hospital Düsseldorf, Medical Faculty of Heinrich Heine University, Germany., Györfi AH; Clinic for Rheumatology (Y.-N.L., A.-E.M., A.-H.G., V.D., A.G., J.H.W.D., M.L.), University Hospital Düsseldorf, Medical Faculty of Heinrich Heine University, Germany.; Hiller Research Center (Y.-N.L., A.-E.M., A.-H.G., V.D., A.G., J.H.W.D., M.L.), University Hospital Düsseldorf, Medical Faculty of Heinrich Heine University, Germany., Bruch PM; Department of Haematology, Oncology and Clinical Immunology, University Hospital Düsseldorf, Germany (P.-M.B., S.K., S.D.).; Center for Integrated Oncology Aachen-Bonn-Cologne-Düsseldorf, Aachen Bonn Cologne, Germany (P.-M.B., S.K., S.D.).; Molecular Medicine Partnership Unit, Heidelberg, Germany (P.-M.B., S.K., S.D.).; Department of Hematology, Oncology and Rheumatology, University Hospital Heidelberg, Germany (P.-M.B., S.D.)., Koziel S; Department of Haematology, Oncology and Clinical Immunology, University Hospital Düsseldorf, Germany (P.-M.B., S.K., S.D.).; Center for Integrated Oncology Aachen-Bonn-Cologne-Düsseldorf, Aachen Bonn Cologne, Germany (P.-M.B., S.K., S.D.).; Molecular Medicine Partnership Unit, Heidelberg, Germany (P.-M.B., S.K., S.D.).; Düsseldorf School of Oncology, Germany (S.K.)., Devakumar V; Clinic for Rheumatology (Y.-N.L., A.-E.M., A.-H.G., V.D., A.G., J.H.W.D., M.L.), University Hospital Düsseldorf, Medical Faculty of Heinrich Heine University, Germany.; Hiller Research Center (Y.-N.L., A.-E.M., A.-H.G., V.D., A.G., J.H.W.D., M.L.), University Hospital Düsseldorf, Medical Faculty of Heinrich Heine University, Germany., Gabrielli A; Clinic for Rheumatology (Y.-N.L., A.-E.M., A.-H.G., V.D., A.G., J.H.W.D., M.L.), University Hospital Düsseldorf, Medical Faculty of Heinrich Heine University, Germany.; Hiller Research Center (Y.-N.L., A.-E.M., A.-H.G., V.D., A.G., J.H.W.D., M.L.), University Hospital Düsseldorf, Medical Faculty of Heinrich Heine University, Germany.; Fondazione di Medicina Molecolare e Terapia Cellulare, Università Politecnica delle Marche, Ancona, Italy (A.G.)., Kreuter A; Department of Dermatology, Venerology and Allergology, Helios St. Johannes Klinik Duisburg, Germany (A.K.).; Department of Dermatology, Venerology and Allergology, Helios St. Elisabeth Klinik Oberhausen, University Witten-Herdecke, Germany (A.K.)., Wang J; Department of Rheumatology, Huashan Hospital (J.W., M.L.), Fudan University, Shanghai, P. R. China.; State Key Laboratory of Genetic Engineering, Collaborative Innovation Center for Genetics and Development, School of Life Sciences, and Human Phenome Institute, Fudan University, Shanghai, P. R. China (J.W.).; Research Unit of Dissecting the Population Genetics and Developing New Technologies for Treatment and Prevention of Skin Phenotypes and Dermatological Diseases (2019RU058), Chinese Academy of Medical Sciences, Shanghai, P. R. China (J.W.)., Dietrich S; Department of Haematology, Oncology and Clinical Immunology, University Hospital Düsseldorf, Germany (P.-M.B., S.K., S.D.).; Center for Integrated Oncology Aachen-Bonn-Cologne-Düsseldorf, Aachen Bonn Cologne, Germany (P.-M.B., S.K., S.D.).; Molecular Medicine Partnership Unit, Heidelberg, Germany (P.-M.B., S.K., S.D.).; Department of Hematology, Oncology and Rheumatology, University Hospital Heidelberg, Germany (P.-M.B., S.D.)., Schett G; Department of Internal Medicine 3, Rheumatology and Clinical Immunology (A.R.R., G.S., J.H.W.D., M.L.), Friedrich-Alexander-University Erlangen-Nürnberg and University Hospital Erlangen, Germany.; Deutsches Zentrum Immuntherapie (A.R.R., G.S., J.H.W.D., M.L.), Friedrich-Alexander-University Erlangen-Nürnberg and University Hospital Erlangen, Germany., Distler JHW; Department of Internal Medicine 3, Rheumatology and Clinical Immunology (A.R.R., G.S., J.H.W.D., M.L.), Friedrich-Alexander-University Erlangen-Nürnberg and University Hospital Erlangen, Germany.; Deutsches Zentrum Immuntherapie (A.R.R., G.S., J.H.W.D., M.L.), Friedrich-Alexander-University Erlangen-Nürnberg and University Hospital Erlangen, Germany.; Clinic for Rheumatology (Y.-N.L., A.-E.M., A.-H.G., V.D., A.G., J.H.W.D., M.L.), University Hospital Düsseldorf, Medical Faculty of Heinrich Heine University, Germany.; Hiller Research Center (Y.-N.L., A.-E.M., A.-H.G., V.D., A.G., J.H.W.D., M.L.), University Hospital Düsseldorf, Medical Faculty of Heinrich Heine University, Germany., Liang M; Department of Internal Medicine 3, Rheumatology and Clinical Immunology (A.R.R., G.S., J.H.W.D., M.L.), Friedrich-Alexander-University Erlangen-Nürnberg and University Hospital Erlangen, Germany.; Deutsches Zentrum Immuntherapie (A.R.R., G.S., J.H.W.D., M.L.), Friedrich-Alexander-University Erlangen-Nürnberg and University Hospital Erlangen, Germany.; Clinic for Rheumatology (Y.-N.L., A.-E.M., A.-H.G., V.D., A.G., J.H.W.D., M.L.), University Hospital Düsseldorf, Medical Faculty of Heinrich Heine University, Germany.; Hiller Research Center (Y.-N.L., A.-E.M., A.-H.G., V.D., A.G., J.H.W.D., M.L.), University Hospital Düsseldorf, Medical Faculty of Heinrich Heine University, Germany.; Department of Rheumatology, Huashan Hospital (J.W., M.L.), Fudan University, Shanghai, P. R. China.; Huashan Rare Disease Center (M.L.), Fudan University, Shanghai, P. R. China.
Jazyk:	angličtina
Zdroj:	Circulation research [Circ Res] 2024 Mar 29; Vol. 134 (7), pp. 875-891. Date of Electronic Publication: 2024 Mar 05.
DOI:	10.1161/CIRCRESAHA.123.323299
Abstrakt:	Background: Systemic sclerosis (SSc) is a connective tissue disease that can serve as a model to study vascular changes in response to inflammation, autoimmunity, and fibrotic remodeling. Although microvascular changes are the earliest histopathologic manifestation of SSc, the vascular pathophysiology remains poorly understood. Methods: We applied spatial proteomic approaches to deconvolute the heterogeneity of vascular cells at the single-cell level in situ and characterize cellular alterations of the vascular niches of patients with SSc. Skin biopsies of patients with SSc and control individuals were analyzed by imaging mass cytometry, yielding a total of 90 755 cells including 2987 endothelial cells and 4096 immune cells. Results: We identified 7 different subpopulations of blood vascular endothelial cells (VECs), 2 subpopulations of lymphatic endothelial cells, and 3 subpopulations of pericytes. A novel population of CD34 + ;αSMA + (α-smooth muscle actin);CD31 + VECs was more common in SSc, whereas endothelial precursor cells were decreased. Co-detection by indexing and tyramide signal amplification confirmed these findings. The microenvironment of CD34 + ;αSMA + ;CD31 + VECs was enriched for immune cells and myofibroblasts, and CD34 + ;αSMA + ;CD31 + VECs expressed markers of endothelial-to-mesenchymal transition. The density of CD34 + ;αSMA + ;CD31 + VECs was associated with clinical progression of fibrosis in SSc. Conclusions: Using spatial proteomics, we unraveled the heterogeneity of vascular cells in control individuals and patients with SSc. We identified CD34 + ;αSMA + ;CD31 + VECs as a novel endothelial cell population that is increased in patients with SSc, expresses markers for endothelial-to-mesenchymal transition, and is located in close proximity to immune cells and myofibroblasts. CD34 + ;αSMA + ;CD31 + VEC counts were associated with clinical outcomes of progressive fibrotic remodeling, thus providing a novel cellular correlate for the crosstalk of vasculopathy and fibrosis. Competing Interests: Disclosures Although no disclosures directly relate to the present study, J.H.W. Distler has consultancy relationships with AbbVie, Active Biotech, AnaMar, ARXX, AstraZeneca, Bayer Pharma, Boehringer Ingelheim, Celgene, Galapagos, Genentech, GSK, Inventiva, Janssen, Novartis, Pfizer, Roche, and UCB. JHWD has received research funding from AnaMar, Argenx, ARXX, BMS, Bayer Pharma, Boehringer Ingelheim, Cantargia, Celgene, CSL Behring, Galapagos, GSK, Inventiva, Kiniksa, Lassen, Sanofi-Aventis, RedX, and UCB. Moreover, J.H.W. Distler is a stock owner of 4D Science and a scientific leader of FibroCure.
Databáze:	MEDLINE
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