학술논문
Disordered T cell-B cell interactions in autoantibody-positive inflammatory arthritis
Document Type
article
Author
Amélie M. Julé; Ki Pui Lam; Maria Taylor; Kacie J. Hoyt; Kevin Wei; Maria Gutierrez-Arcelus; Siobhan M. Case; Mia Chandler; Margaret H. Chang; Ezra M. Cohen; Fatma Dedeoglu; Olha Halyabar; Jonathan Hausmann; Melissa M. Hazen; Erin Janssen; Jeffrey Lo; Mindy S. Lo; Esra Meidan; Jordan E. Roberts; Holly Wobma; Mary Beth F. Son; Robert P. Sundel; Pui Y. Lee; Peter T. Sage; Talal A. Chatila; Peter A. Nigrovic; Deepak A. Rao; Lauren A. Henderson
Source
Frontiers in Immunology, Vol 13 (2023)
Subject
Language
English
ISSN
1664-3224
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.