Upregulated TCF1+ Treg Cells With Stronger Function in Systemic Lupus Erythematosus Through Activation of the Wnt-β-Catenin

Abstract

The role of T-cell factor 1 (TCF1) in human regulatory T cells (Treg) and its clinical significance in systemic lupus erythematosus (SLE) remain unclear. Through bioinformatics analysis and flow cytometry, the Tcf7 gene and TCF1 protein were found to be highly expressed in Treg cells. TCF1⁺ Treg cells exhibited increased expression of CTLA4 and LAG3 and higher IL-10 secretion than TCF1⁻ Treg cells. Circulating TCF1⁺ Treg cells were elevated and displayed increased inhibitory markers in SLE patients. The Wnt-β-catenin pathway was activated in TCF1⁺ Treg cells in SLE patients. The addition of XAV939 impaired the function of TCF1⁺ Treg cells. Clinically, TCF1⁺ Treg cells were not only related to CRP, ESR and IL-2, but also could differentiate SLE patients from healthy controls, primary Sjögren's syndrome patients and rheumatoid arthritis patients. In conclusion, the increased TCF1⁺ Treg cells in SLE patients indicate a stronger suppressive function for the activated Wnt-β-catenin pathway and help screening and assisting in the diagnosis of SLE patients.