Author:
Julé Amélie M.,Lam Ki Pui,Taylor Maria,Hoyt Kacie J.,Wei Kevin,Gutierrez-Arcelus Maria,Case Siobhan M.,Chandler Mia,Chang Margaret H.,Cohen Ezra M.,Dedeoglu Fatma,Halyabar Olha,Hausmann Jonathan,Hazen Melissa M.,Janssen Erin,Lo Jeffrey,Lo Mindy S.,Meidan Esra,Roberts Jordan E.,Wobma Holly,Son Mary Beth F.,Sundel Robert P.,Lee Pui Y.,Sage Peter T.,Chatila Talal A.,Nigrovic Peter A.,Rao Deepak A.,Henderson Lauren A.
Abstract
T peripheral helper (Tph) cells, identified in the synovium of adults with seropositive rheumatoid arthritis, drive B cell maturation and antibody production in non-lymphoid tissues. We sought to determine if similarly dysregulated T cell-B cell interactions underlie another form of inflammatory arthritis, juvenile oligoarthritis (oligo JIA). Clonally expanded Tph cells able to promote B cell antibody production preferentially accumulated in the synovial fluid (SF) of oligo JIA patients with antinuclear antibodies (ANA) compared to autoantibody-negative patients. Single-cell transcriptomics enabled further definition of the Tph gene signature in inflamed tissues and showed that Tph cells from ANA-positive patients upregulated genes associated with B cell help to a greater extent than patients without autoantibodies. T cells that co-expressed regulatory T and B cell-help factors were identified. The phenotype of these Tph-like Treg cells suggests an ability to restrain T cell-B cell interactions in tissues. Our findings support the central role of disordered T cell-help to B cells in autoantibody-positive arthritides.
Funder
National Institute of Arthritis and Musculoskeletal and Skin Diseases
Burroughs Wellcome Fund
Charles H. Hood Foundation
Rheumatology Research Foundation
Arthritis National Research Foundation
Subject
Immunology,Immunology and Allergy