CD3 downregulation on T-cells is concomitant with arginase upregulation on myeloid cells in the synovial fluid of patients with juvenile idopathic arthritis

Abstract

Abstract Rationale Juvenile idiopathic arthritis (JIA) is an inflammatory autoimmune disorder driven by dysfunction of the joint tissue and abnormal immune responses. As deep phenotyping of synovial fluid (SF) might yield new targetable mechanisms of inflammation in JIA patients, we initiated the Emory Multi Omics JIA Immunology (EMOJI) project. Methods Patients with JIA between the ages of 6 and 18 were consented and enrolled for collection of SF from the knee and venous blood. Blood and SF leukocytes were analyzed by flow cytometry. Platelet-free plasma and debris-free SF supernatant were obtained by dual centrifugation and a 20-plex chemiluminescent assay (Meso Scale Discovery) was used to quantify cytokines. Results We report data on blood and SF collected at the same visit from 7 JIA patients. JIA subtypes represented were psoriatic (N=1), oligoarticular extended (N=1), oligoarticular persistent (N=2) and polyarticular (N=3) arthritis; all rheumatoid factor-negative. CD3 expression was decreased on SF compared to blood T-cells. Concomitantly, expression of the CD3-inhibitory enzyme arginase was increased on SF compared to blood neutrophils and macrophages. However, arginase-rich primary granules were not significantly exocytosed by SF neutrophils. Finally, we measured high levels of neutrophil chemoattractants (IL-8, G-CSF, and IL-1α) in SF compared to plasma. Conclusions Neutrophils are recruited to the joints of JIA patients and accumulate arginase on their surface, presumably released from tertiary, but not primary, granules. Arginase activity in the SF may lead to CD3 downregulation and T-cell inhibition, potentially in an effort to limit autoimmune complications.