There is an urgent need for alternative therapies targeting human dendritic cells (DCs) that could reverse inflammatory syndromes in many autoimmune and inflammatory diseases and organ transplantations. Here, we describe a bispecific antibody (bsAb) strategy tethering two pathogen-recognition receptors at the surface of human DCs. This cross-linking switches DCs into a tolerant profile able to induce regulatory T-cell differentiation. The bsAbs, not parental Abs, induced interleukin 10 and transforming growth factor β1 secretion in monocyte-derived DCs and human peripheral blood mononuclear cells. In addition, they induced interleukin 10 secretion by synovial fluid cells in rheumatoid arthritis and gout patients. This concept of bsAb-induced tethering of surface pathogen-recognition receptors switching cell properties opens a new therapeutic avenue for controlling inflammation and restoring immune tolerance.
Keywords: TGF-β1; TLR2; bispecific antibody; human dendritic cell; innate receptors; interleukine-10; tolerant dendritic cell; type C lectin.
Copyright © 2024 Lamendour, Gilotin, Deluce-Kakwata Nkor, Lakhrif, Meley, Poupon, Laboute, di Tommaso, Pin, Mulleman, Le Mélédo, Aubrey, Watier and Velge-Roussel.