Background/Aims: 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 clinical samples and healthy controls. Results: 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. Conclusion: Taken together, our findings indicate that CD4+CD25hiCD127low/-Foxp3+Helios+ may represent the real Treg cell population in patients with RA.

No abstract

Fibroblast-like synoviocytes (FLSs) are the predominant effector cells in the pathological progression of rheumatoid arthritis (RA). Therefore, elucidating the underlying molecular mechanism of the biologic behaviors in RA-FLSs will be helpful in developing the potent targets for the treatment of RA. We have previously documented that the tumor-like biologic behaviors of RA-FLSs are exacerbated by urokinase-type plasminogen activator receptor (uPAR), a specifically up-regulated receptor in RA-FLSs.Here, we investigate the further mechanism of uPAR and clarify its function in RA-FLSs. We demonstrate that miR-221-3p positively correlates to uPAR and regulates uPAR level in RA-FLSs. Simultaneously, one long noncoding RNA, nuclear paraspeckle assembly transcript 1_1 (NEAT1_1) is identified, which can predictively target miR-221-3p at three sites, indicating a strong possibility of being a competing endogenous RNA in RA-FLSs. Interestingly, NEAT1_1 and miR-221-3p can colocate in the nucleus and cytoplasm in RA-FLSs. Importantly, NEAT1_1 can act as a rheostat for the miR-221-3p/uPAR axis and the downstream JAK signaling. In line with the biologic function, NEAT1_1 negatively regulates the tumor-like characters, and cytokine secretions of RA-FLSs. Collectively, our data provide new insight into the mechanisms of NEAT1_1 in modulating RA-FLSs tumor-like behaviors. The targeting of NEAT1_1 and miR-221-3p/uPAR axis may have a promising therapeutic role in patients with RA.