FCRL3 expression is upregulated and closely correlates with TIGIT expression in regulatory T cells of patients with systemic lupus erythematosus

Abstract

FCRL3 expression is upregulated and closely correlates with TIGIT expression in regulatory T cells of patients with systemic lupus erythematosusHuman Fc receptor-like 3 (FCRL3), also known as CD307c, is a cell surface receptor homologous to the Fc immunoreceptor. It is mainly expressed in B lymphocytes but also Treg cells, CD8 + T cells, NK cells, and other lymphocyte subsets [1,2,3]. FCRL3 can negatively modulate Tcell receptor (TCR) signaling in Treg cells [4] and inhibit their function via secretory immunoglobulin A, a potential ligand of FCRL3 [5]. In a study of rheumatoid arthritis, FCRL3 + Treg cells were found to be less inhibitory than FCRL3 -Treg cells [4]. FCRL3 has been identified as a susceptibility gene for SLE [6]. However, whether FCRL3 is dysregulated in Treg cells from SLE patients remains unknown.In this study, we first investigated the expression of FCRL3 in T-cell subsets. Based on single-cell RNA sequencing (scRNA-Seq) data analysis, FCRL3 was highly expressed in Treg cells (Supporting information Fig. S1). In CD4 + T-cell subsets defined by CXCR5 and FoxP3 expression in HCs, the proportion of FCRL3 + cells in Treg cells was significantly higher than in conventional T (Con-T) cells (Supporting information Fig. S2).Analysis of the scRNA-Seq data revealed that FCRL3 expression was increased in either CD4 + T cells or Treg cells from children or adult patients (Fig. 1A and B). Therefore, we recruited 64 patients with SLE and 64 HCs (Supporting information Table S1) and the results showed that the percentage of