Helios But Not CD226, TIGIT and Foxp3 is a Potential Marker for CD4 Treg Cells in Patients with Rheumatoid Arthritis

Abstract

Background: Rheumatoid arthritis (RA) is a progressive, chronic, even disabling systemic autoimmune disease. Imbalance between pathogenic immune cells and immunosuppressive cells is associated with the pathogenesis and development of RA and other autoimmune diseases. As Foxp3 is also expressed on activated CD4 cells in the presence of inflammation, the identification of Treg cells in patients with RA remains a challenge. Methods: Comprehensive analyses were carried out by Flow cytometry. Expression of Helios, CD226, T cell immunoreceptor with Ig and ITIM domains (TIGIT) was analyzed by clinical samples of rheumatoid arthritis patients and healthy controls. Findings: we have systemically examined three potential markers, Helios, CD226 and TIGIT that are possibly related to Treg identification, and found that Helios expression on CD4 Foxp3 cells was decreased and negatively correlated with the disease activity of RA patients, while CD226 and TIGIT both showed elevated expression levels in CD4 Foxp3 cells in RA patients and they were not associated with disease activity of RA patients. Interpretation: Our findings indicate that CD4 CD25hiCD127low/-Foxp3 Helios may represent the real Treg cell population in patients with RA. Funding: This work was supported in part by grants from the National Key R&D Program of China (2017YFA0105800), General Program of National Natural Science Foundation of China (81671611) and the Zhujiang Innovative and Entrepreneurial Talent Team Award of Guangdong Province (2016 ZT 06S 252) and NIH R01 AR 059103. Declaration of Interest: All authors have no conflict of interest. Ethical Approval: All human studies have been approved by the Research Ethical Committee of the Third Affiliated Hospital at Sun Yat-sen University. Before study, written informed consents were received from all participants.