Distinct tissue-niche localization and function of synovial tissue myeloid DC subsets in health, and in active and remission Rheumatoid Arthritis
Lucy MacDonald1.2# and Aziza Elmesmari1.2# and Domenico Somma1.2# and Jack Frew1.2#, Clara Di Mario3, Roopa Madhu4,5,6, Audrey Paoletti2, Theodoros Simakou1,2, Olympia Hardy1,2, Barbara Tolusso3, Denise Campobasso3, Simone Perniola3,7, Marco Gessi8, Maria Rita Gigante9, Luca Petricca9, Dario Bruno1,3,7, Roberta Benvenuto8, John D. Isaacs1,10,11, Andrew Filby12, David McDonald12, Jasmine P. X. Sim1,10, Kevin Wei4, Maria Antonietta D’Agostino9, Neal L. Millar1,2, Simon Milling1,2, Charles McSharry2, Elisa Gremese1,3,7, Karen Affleck13, Kenneth F. Baker1,10,11, Iain B. McInnes1,2, Thomas D. Otto1,2, Ilya Korsunsky4,5,6, Stefano Alivernini1,2,3,9 and Mariola Kurowska-Stolarska1,2,
1 Research into Inflammatory Arthritis Centre Versus Arthritis (RACE), Glasgow, Birmingham, Newcastle, and Oxford, United Kingdom. 2 School of Infection & Immunity, University of Glasgow, United Kingdom, 3 Immunology Research Core Facility, Gemelli Science and Technology Park, Fondazione Policlinico Universitario A. Gemelli IRCCS, Rome, Italy. 4 Division of Rheumatology, Inflammation, and Immunity, Brigham and Women's Hospital and Harvard Medical School, Boston, MA 02115, USA 5 Division of Genetics, Department of Medicine, Brigham and Women's Hospital, Boston, MA 02115, USA 6 Broad Institute of MIT and Harvard, Cambridge, MA 02141, USA 7 Division of Clinical Immunology, Fondazione Policlinico Universitario A. Gemelli IRCCS, Rome, Italy. 8 Institute of Pathology, Fondazione Policlinico Universitario A. Gemelli IRCCS, Rome, Italy. 9 Division of Rheumatology, Fondazione Policlinico Universitario A. Gemelli IRCCS, Rome, Italy. 10 Translational and Clinical Research Institute, Newcastle University, Newcastle upon Tyne, United Kingdom 11 Musculoskeletal Unit, Newcastle-upon-Tyne Hospitals, Newcastle upon Tyne, United Kingdom 12 Flow Cytometry Core Facility, Newcastle University, Newcastle upon Tyne, United Kingdom 13 Respiratory and Immunology Research Unit, GSK, Stevenage, United Kingdom
Equally contributing first# and last@ authors
*Corresponding authors: Stefano Alivernini: stefano.alivernini@unicatt.it Mariola Kurowska-Stolarska: Mariola.Kurowska-Stolarska@glasgow.ac.uk
This repository contains notebooks with code for the analysis of whole transcriptome and targetted single-cell RNA sequencing (scRNAseq) and cellular indexing of transcriptomes and protein epitopes sequencing (CITEseq) of peripheral blood and synovial tissue from healthy donors, and Rheumatoid Arthritis (RA) patients with active disease or sustained clinical remission. Together spatial transcriptomics (https://github.com/DrLucyMac/spatial_synoDC/) and micro-coculture of synovial tissue DC clusters with autologous T-cells, we identified the critical niches that determine DC subset/T-cell subset interactions in RA. These studies establish hierarchies of interaction for naïve-T-cells, TEM, and TPH maturation driven by geographically discrete DC subsets in the pathogenesis of RA, setting the stage for novel therapeutic interventions.