1. Disordered T cell-B cell interactions in autoantibody-positive inflammatory arthritis
- Author
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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, and Lauren A. Henderson
- Subjects
Immunology ,Immunology and Allergy - 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.
- Published
- 2023
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