AB0358 Umbilical cord mesenchymal stem cells inhibit the generation of t follicular helper cell in rheumatoid arthritis

Abstract

Background The immune suppressive properties of mesenchymal stem cells (MSCs) have garnered increasing attention over the past decades. MSCs that derived from human umbilical cord (UC) share similar immunosuppressive properties as MSCs obtained from bone marrow and cord blood in vitro. Rheumatoid arthritis (RA) is characterized by persistent synovitis and systemic inflammation, frequently leading to cartilage and bone destruction. Previous studies showed that MSCs transplantation had effect in an animal model of RA. However, the mechanism remains largely unknown. Objectives The purpose of this study was to confirm the hypothesis that UC-MSCs might suppress the generation of T follicular helper (Tfh) cells in RA patients. Methods The percentages of CXCR5+PD-1+CD4+ cells were analyzed by flow cytometry in peripheral blood mononuclear cells (PBMC) from RA patients and healthy controls. PBMC from RA patients stimulated with or without phytoagglutinin (PHA) were cultured with UC-MSCs supernatant or UC-MSCs at a ratio of 1 to 1, 1 to 10 or 1 to 100 in a cell-to-cell contact or in a transwell system for 3 days. Naïve T cells were isolated from PBMC of RA patients and then co-cultured with UC-MSC in the presence of anti-CD3, anti-CD28, anti-IFNg, anti-IL-4, anti-TGFb, IL-6, IL-21 and IL-12 for 4 days. The percentages of CXCR5+PD-1+CD4+ cells were tested by means of flow cytometry. Results The results showed that the circulating percentages of CXCR5+PD-1+CD4+ cells were significantly higher than that of healthy controls. UC-MSCs did not inhibit non-activated Tfh cells but dose-dependently inhibited the generation of Tfh cells when stimulated with PHA whether in a cell-to-cell contact or in a transwell system. The differentiation of Tfh cells were also blocked by UC-MSCs significantly. However, UC-MSCs supernatant was not able to suppress the generation of Tfh cells in RA. Conclusions These results suggest an inhibitory effect of UC-MSCs on the generation of Tfh cells via soluble factors secreted from UC-MSCs, which may be one the mechanism of UC-MSCs treatment in RA. Disclosure of Interest None Declared