Frontiers in Immunology (Jan 2023)
Disordered T cell-B cell interactions in autoantibody-positive inflammatory arthritis
- Amélie M. Julé,
- Ki Pui Lam,
- Maria Taylor,
- Kacie J. Hoyt,
- Kevin Wei,
- Maria Gutierrez-Arcelus,
- Maria Gutierrez-Arcelus,
- Maria Gutierrez-Arcelus,
- Siobhan M. Case,
- Siobhan M. Case,
- Mia Chandler,
- Margaret H. Chang,
- Margaret H. Chang,
- Ezra M. Cohen,
- 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,
- Pui Y. Lee,
- Peter T. Sage,
- Talal A. Chatila,
- Peter A. Nigrovic,
- Peter A. Nigrovic,
- Deepak A. Rao,
- Lauren A. Henderson
Affiliations
- Amélie M. Julé
- Division of Immunology, Boston Children’s Hospital, Harvard Medical School, Boston, MA, United States
- Ki Pui Lam
- Division of Immunology, Boston Children’s Hospital, Harvard Medical School, Boston, MA, United States
- Maria Taylor
- Division of Immunology, Boston Children’s Hospital, Harvard Medical School, Boston, MA, United States
- Kacie J. Hoyt
- Division of Immunology, Boston Children’s Hospital, Harvard Medical School, Boston, MA, United States
- Kevin Wei
- Division of Rheumatology, Inflammation, and Immunity, Brigham and Women’s Hospital, Harvard Medical School, Boston, MA, United States
- Maria Gutierrez-Arcelus
- Division of Immunology, Boston Children’s Hospital, Harvard Medical School, Boston, MA, United States
- Maria Gutierrez-Arcelus
- Division of Rheumatology, Inflammation, and Immunity, Brigham and Women’s Hospital, Harvard Medical School, Boston, MA, United States
- Maria Gutierrez-Arcelus
- Broad Institute of Massachusetts Institute of Technology (MIT) and Harvard, Cambridge, MA, United States
- Siobhan M. Case
- Division of Immunology, Boston Children’s Hospital, Harvard Medical School, Boston, MA, United States
- Siobhan M. Case
- Division of Rheumatology, Inflammation, and Immunity, Brigham and Women’s Hospital, Harvard Medical School, Boston, MA, United States
- Mia Chandler
- Division of Immunology, Boston Children’s Hospital, Harvard Medical School, Boston, MA, United States
- Margaret H. Chang
- Division of Immunology, Boston Children’s Hospital, Harvard Medical School, Boston, MA, United States
- Margaret H. Chang
- Division of Rheumatology, Inflammation, and Immunity, Brigham and Women’s Hospital, Harvard Medical School, Boston, MA, United States
- Ezra M. Cohen
- Division of Immunology, Boston Children’s Hospital, Harvard Medical School, Boston, MA, United States
- Ezra M. Cohen
- Division of Rheumatology, Boston Medical Center, Boston University School of Medicine, Boston, MA, United States
- Fatma Dedeoglu
- Division of Immunology, Boston Children’s Hospital, Harvard Medical School, Boston, MA, United States
- Olha Halyabar
- Division of Immunology, Boston Children’s Hospital, Harvard Medical School, Boston, MA, United States
- Jonathan Hausmann
- Division of Immunology, Boston Children’s Hospital, Harvard Medical School, Boston, MA, United States
- Melissa M. Hazen
- Division of Immunology, Boston Children’s Hospital, Harvard Medical School, Boston, MA, United States
- Erin Janssen
- Division of Immunology, Boston Children’s Hospital, Harvard Medical School, Boston, MA, United States
- Jeffrey Lo
- Division of Immunology, Boston Children’s Hospital, Harvard Medical School, Boston, MA, United States
- Mindy S. Lo
- Division of Immunology, Boston Children’s Hospital, Harvard Medical School, Boston, MA, United States
- Esra Meidan
- Division of Immunology, Boston Children’s Hospital, Harvard Medical School, Boston, MA, United States
- Jordan E. Roberts
- Division of Immunology, Boston Children’s Hospital, Harvard Medical School, Boston, MA, United States
- Holly Wobma
- Division of Immunology, Boston Children’s Hospital, Harvard Medical School, Boston, MA, United States
- Mary Beth F. Son
- Division of Immunology, Boston Children’s Hospital, Harvard Medical School, Boston, MA, United States
- Robert P. Sundel
- Division of Immunology, Boston Children’s Hospital, Harvard Medical School, Boston, MA, United States
- Pui Y. Lee
- Division of Immunology, Boston Children’s Hospital, Harvard Medical School, Boston, MA, United States
- Pui Y. Lee
- Division of Rheumatology, Inflammation, and Immunity, Brigham and Women’s Hospital, Harvard Medical School, Boston, MA, United States
- Peter T. Sage
- Transplantation Research Center, Renal Division, Brigham and Women’s Hospital, Harvard Medical School, Boston, MA, United States
- Talal A. Chatila
- Division of Immunology, Boston Children’s Hospital, Harvard Medical School, Boston, MA, United States
- Peter A. Nigrovic
- Division of Immunology, Boston Children’s Hospital, Harvard Medical School, Boston, MA, United States
- Peter A. Nigrovic
- Division of Rheumatology, Inflammation, and Immunity, Brigham and Women’s Hospital, Harvard Medical School, Boston, MA, United States
- Deepak A. Rao
- Division of Rheumatology, Inflammation, and Immunity, Brigham and Women’s Hospital, Harvard Medical School, Boston, MA, United States
- Lauren A. Henderson
- Division of Immunology, Boston Children’s Hospital, Harvard Medical School, Boston, MA, United States
- DOI
- https://doi.org/10.3389/fimmu.2022.1068399
- Journal volume & issue
-
Vol. 13
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.
Keywords
- T cells
- autoimmunity
- autoantibodies
- juvenile idiopathic arthritis
- T peripheral helper cell
- regulatory T (Treg) cell
