Treg Cells Implicated in JIA

Researchers have found a subset of Treg cells that are more prevalent in the blood of patients with juvenile idiopathic arthritis and active inflammation, as compared to patients in remission.

The findings have a potential impact for both rheumatoid arthritis as well as oligoarticular and polyarticular juvenile idiopathic arthritis. The study, which was led by Maura Rossetti of the University of California Los Angeles and the SingHealth and Duke-NUS Graduate Medical School in Singapore, appears in the June 16 issue of the Annals of the Rheumatic Diseases.

“Our work uncovers an easily accessible pool of synovial Treg cells in circulation that might be used as a novel non-invasive diagnostic tool, and proposes an innovative antigen-agnostic approach to shed light on pathogenic mechanisms of autoimmune disease and unresponsiveness to therapy,” researchers wrote.

The imbalance between regulatory T cells and effector cells is linked to the pathogenesis of autoimmune arthritis.

“Immune responses are often investigated in the blood because of its accessibility, but circulating lymphocytes are not representative of those found in inflamed tissues. This disconnect hinders our understanding of the mechanisms underlying disease. Our goal was to identify Treg cells implicated in autoimmunity at the inflamed joints, and also readily detectable in the blood upon recirculation,” the authors wrote.

In rheumatoid arthritis, regulatory T cells are believed to be lower in number and dysfunctional. Some therapies, such as anti-tumor necrosis factor, can help to reestablish normal regulatory T cell counts and function, the authors reported. Most studies agree that in juvenile idiopathic arthritis, regulatory T cells accumulate in the synovial fluid.  [[{"type":"media","view_mode":"media_crop","fid":"49680","attributes":{"alt":"©PuwadolJaturawutthichai/Shutterstock.com","class":"media-image media-image-right","id":"media_crop_6009444552164","media_crop_h":"0","media_crop_image_style":"-1","media_crop_instance":"6022","media_crop_rotate":"0","media_crop_scale_h":"0","media_crop_scale_w":"0","media_crop_w":"0","media_crop_x":"0","media_crop_y":"0","style":"font-size: 13.008px; line-height: 1.538em; float: right;","title":"©PuwadolJaturawutthichai/Shutterstock.com","typeof":"foaf:Image"}}]]

The authors compared regulatory T cells from patients with juvenile idiopathic arthritis who were or were not responding to therapy by using T cell receptor sequencing, FOXP3 regulatory T cell-specific demethylated region methylation assays, flow cytometry and suppression assays.

They found a subset of synovial regulatory T cells that recirculated into the bloodstream. “These inflammation-associated Treg cells, but not other blood Treg cells, expanded during active disease and proliferated in respond to their cognate antigens,” the authors wrote. The idiopathic arthritis regulatory cells were stably committed to their regulatory lineage, and they were fully suppressive.

“The consistency of our findings in two distinct autoimmune diseases highlights the clinical relevance of iaTreg cells in conditions where immune regulation is ineffective,” the authors wrote. “Further investigations of this subset may yield critical insights into the pathological mechanisms at play in human arthritis and, possibly, autoimmunity at large.”

References:

Rossetti M, Spreafico R, Consolaro A, et al. “TCR repertoire sequencing identifies synovial Treg cell clonotypes in the bloodstream during active inflammation in human arthritis.” Ann Rheum Dis. 2016 Jun 16. pii: annrheumdis-2015-208992. doi: 10.1136/annrheumdis-2015-208992.