Identification of a Distinct Monocyte‐Driven Signature in Systemic Sclerosis Using Biophysical Phenotyping of Circulating Immune Cells

Pathologically activated circulating immune cells, including monocytes, play major roles in systemic sclerosis (SSc). Their functional characterization can provide crucial information with direct clinical relevance. However, tools for the evaluation of pathologic immune cell activation and, in general, of clinical outcomes in SSc are scarce. Biophysical phenotyping (including characterization of cell mechanics and morphology) provides access to a novel, mostly unexplored layer of information regarding pathophysiologic immune cell activation. We hypothesized that the biophysical phenotyping of circulating immune cells, reflecting their pathologic activation, can be used as a clinical tool for the evaluation and risk stratification of patients with SSc.

[1]  G. Schett,et al.  68Ga-FAPI-04 PET-CT for molecular assessment of fibroblast activation and risk evaluation in systemic sclerosis-associated interstitial lung disease: a single-centre, pilot study. , 2021, The Lancet. Rheumatology.

[2]  J. Guck,et al.  Physical phenotype of blood cells is altered in COVID-19 , 2021, bioRxiv.

[3]  A. Antanaviciute,et al.  Targeting human plasmacytoid dendritic cells through BDCA2 prevents skin inflammation and fibrosis in a novel xenotransplant mouse model of scleroderma , 2021, Annals of the Rheumatic Diseases.

[4]  S. Saidin,et al.  Systemic Sclerosis Perturbs the Architecture of the Immunome , 2020, Frontiers in Immunology.

[5]  J. Guck,et al.  Intelligent image-based deformation-assisted cell sorting with molecular specificity , 2020, Nature Methods.

[6]  W. Marut,et al.  Novel insights into dendritic cells in the pathogenesis of systemic sclerosis , 2020, Clinical and experimental immunology.

[7]  J. Guck,et al.  The mechanics of myeloid cells , 2020, Biology of the cell.

[8]  L. Kanz,et al.  Invariant natural killer T cells are functionally impaired in patients with systemic sclerosis , 2019, Arthritis Research & Therapy.

[9]  M. Whitfield,et al.  Shared and distinct mechanisms of fibrosis , 2019, Nature Reviews Rheumatology.

[10]  S. Walsh,et al.  Nintedanib in Progressive Fibrosing Interstitial Lung Diseases. , 2019, The New England journal of medicine.

[11]  Madeleine K. D. Scott,et al.  Increased monocyte count as a cellular biomarker for poor outcomes in fibrotic diseases: a retrospective, multicentre cohort study , 2019, The Lancet. Respiratory medicine.

[12]  L. Menschner,et al.  Real‐time deformability cytometry reveals sequential contraction and expansion during neutrophil priming , 2019, Journal of leukocyte biology.

[13]  P. Kuppen,et al.  Characterization of circulating T-, NK-, and NKT cell subsets in patients with colorectal cancer: the peripheral blood immune cell profile , 2019, Cancer Immunology, Immunotherapy.

[14]  O. Distler,et al.  Involvement of the myeloid cell compartment in fibrogenesis and systemic sclerosis , 2019, Nature Reviews Rheumatology.

[15]  David R. Myers,et al.  The biophysics and mechanics of blood from a materials perspective , 2019, Nature Reviews Materials.

[16]  Anna V. Taubenberger,et al.  Spheroid Culture of Mesenchymal Stromal Cells Results in Morphorheological Properties Appropriate for Improved Microcirculation , 2019, Advanced science.

[17]  M. Reynaud‐Gaubert,et al.  Natural Killer Cells Exhibit a Peculiar Phenotypic Profile in Systemic Sclerosis and Are Potent Inducers of Endothelial Microparticles Release , 2018, Front. Immunol..

[18]  Oliver Otto,et al.  Real-time fluorescence and deformability cytometry , 2018, Nature Methods.

[19]  J. Distler,et al.  Targeting TGF-β signaling for the treatment of fibrosis. , 2018, Matrix biology : journal of the International Society for Matrix Biology.

[20]  L. Menschner,et al.  Detection of human disease conditions by single-cell morpho-rheological phenotyping of blood , 2018, eLife.

[21]  Anna V. Taubenberger,et al.  Single-cell mechanical phenotype is an intrinsic marker of reprogramming and differentiation along the mouse neural lineage , 2017, Development.

[22]  Sheng Yang Michael Loh,et al.  Large‐scale image‐based screening and profiling of cellular phenotypes , 2017, Cytometry. Part A : the journal of the International Society for Analytical Cytology.

[23]  M. Baron,et al.  The European Scleroderma Trials and Research group (EUSTAR) task force for the development of revised activity criteria for systemic sclerosis: derivation and validation of a preliminarily revised EUSTAR activity index , 2016, Annals of the rheumatic diseases.

[24]  David R. Myers,et al.  Cellular softening mediates leukocyte demargination and trafficking, thereby increasing clinical blood counts , 2016, Proceedings of the National Academy of Sciences.

[25]  W. Marut,et al.  Update on biomarkers in systemic sclerosis: tools for diagnosis and treatment , 2015, Seminars in Immunopathology.

[26]  Alain Richert,et al.  Human Primary Immune Cells Exhibit Distinct Mechanical Properties that Are Modified by Inflammation. , 2015, Biophysical journal.

[27]  U. Keyser,et al.  Real-time deformability cytometry: on-the-fly cell mechanical phenotyping , 2015, Nature Methods.

[28]  Jochen Guck,et al.  Mechanics Meets Medicine , 2013, Science Translational Medicine.

[29]  Yo Sup Moon,et al.  Quantitative Diagnosis of Malignant Pleural Effusions by Single-Cell Mechanophenotyping , 2013, Science Translational Medicine.

[30]  M. Hallett,et al.  Ca2+ and calpain control membrane expansion during the rapid cell spreading of neutrophils , 2013, Journal of Cell Science.

[31]  Yanfang Jiang,et al.  Increased Numbers of NK Cells, NKT-Like Cells, and NK Inhibitory Receptors in Peripheral Blood of Patients with Chronic Obstructive Pulmonary Disease , 2013, Clinical & developmental immunology.

[32]  M. Matucci-Cerinic,et al.  Review: evidence that systemic sclerosis is a vascular disease. , 2013, Arthritis and rheumatism.

[33]  D. Vergani,et al.  CD14, CD16 and HLA‐DR reliably identifies human monocytes and their subsets in the context of pathologically reduced HLA‐DR expression by CD14hi/CD16neg monocytes: Expansion of CD14hi/CD16pos and contraction of CD14lo/CD16pos monocytes in acute liver failure , 2012, Cytometry. Part A : the journal of the International Society for Analytical Cytology.

[34]  Jochen Guck,et al.  Viscoelastic Properties of Differentiating Blood Cells Are Fate- and Function-Dependent , 2012, PloS one.

[35]  T. Hügle,et al.  T cells in systemic sclerosis: a reappraisal. , 2012, Rheumatology.

[36]  Dino Di Carlo,et al.  A Mechanical Biomarker of Cell State in Medicine , 2012, Journal of laboratory automation.

[37]  Miho Suzuki,et al.  IL-6/IL-6 receptor system and its role in physiological and pathological conditions. , 2012, Clinical science.

[38]  P. Lachenbruch,et al.  Skin score. A semiquantitative measure of cutaneous involvement that improves prediction of prognosis in systemic sclerosis. , 2010, Arthritis and rheumatism.

[39]  S. Jimenez,et al.  As submitted to : Biomarkers in Medicine And later published as : “ Biomarkers in Systemic Sclerosis ” , 2017 .

[40]  Daniel A. Fletcher,et al.  Cell mechanics and the cytoskeleton , 2010, Nature.

[41]  Stefan Schinkinger,et al.  The regulatory role of cell mechanics for migration of differentiating myeloid cells , 2009, Proceedings of the National Academy of Sciences.

[42]  C. Chizzolini T cells, B cells, and polarized immune response in the pathogenesis of fibrosis and systemic sclerosis , 2008, Current opinion in rheumatology.

[43]  Daniel A Fletcher,et al.  Analyzing cell mechanics in hematologic diseases with microfluidic biophysical flow cytometry. , 2008, Lab on a chip.

[44]  D. Hansell,et al.  Interstitial lung disease in systemic sclerosis: a simple staging system. , 2008, American journal of respiratory and critical care medicine.

[45]  F Verrecchia,et al.  [Cellular and molecular mechanisms of fibrosis]. , 2006, Annales de pathologie.

[46]  R. Kondo,et al.  Neutrophil cytoskeletal rearrangements during capillary sequestration in bacterial pneumonia in rats. , 2006, American journal of respiratory and critical care medicine.

[47]  Jochen Guck,et al.  High-throughput single-cell mechanical phenotyping with real-time deformability cytometry. , 2018, Methods in cell biology.

[48]  Oliver Otto,et al.  Real-Time Deformability Cytometry: Label-Free Functional Characterization of Cells. , 2018, Methods in molecular biology.