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.
Keywords: T cells; T peripheral helper cell; autoantibodies; autoimmunity; juvenile idiopathic arthritis; regulatory T (Treg) cell.
Copyright © 2023 Julé, Lam, Taylor, Hoyt, Wei, Gutierrez-Arcelus, Case, Chandler, Chang, Cohen, Dedeoglu, Halyabar, Hausmann, Hazen, Janssen, Lo, Lo, Meidan, Roberts, Wobma, Son, Sundel, Lee, Sage, Chatila, Nigrovic, Rao and Henderson.