Siglec-9 is upregulated in rheumatoid arthritis and suppresses collagen-induced arthritis through reciprocal regulation of Th17-/Treg-cell differentiation

Abstract

Sialic acid-binding Ig-like lectin-9 (Siglec-9) is a novel sialic acid-binding member of the immunoglobulin superfamily and is broadly expressed on immune cells, which can inhibit both innate and adaptive immune responses through immunoreceptor tyrosine-based inhibitory motifs. However, the exact role of Siglec-9 in the pathogenesis of rheumatoid arthritis (RA) remains unknown. In this study, we determined soluble Siglec-9 (sSiglec-9) levels in the serum and synovial fluid of patients with RA and evaluated the relation between sSiglec-9 levels and clinical factors. In addition, we investigated whether Siglec-9 could alleviate collagen-induced arthritis (CIA) development in mice and explored the molecular mechanisms involved. The results showed that, in the serum and synovial fluid of patients with RA, sSiglec-9 levels were elevated. Thus, high sSiglec-9 serum levels associated with disease severity in patients with RA. Furthermore, administration of recombinant human Siglec-9 Fc chimera protein significantly attenuated collagen-induced arthritis development in vivo and in vitro by reciprocal regulation of the differentiation of Th17 and Treg cells. Our findings collectively indicate that Siglec-9 plays a potent immunosuppressive role in the pathogenesis of RA by reciprocal regulation of Th17-/Treg-cell differentiation. In conclusion, Siglec-9 may serve as a potential diagnostic and therapeutic target for RA.