AUTHOR=Lamendour Lucille , Gilotin Mäelle , Deluce-Kakwata Nkor Nora , Lakhrif Zineb , Meley Daniel , Poupon Anne , Laboute Thibaut , di Tommaso Anne , Pin Jean-Jacques , Mulleman Denis , Le Mélédo Guillaume , Aubrey Nicolas , Watier Hervé , Velge-Roussel Florence TITLE=Bispecific antibodies tethering innate receptors induce human tolerant-dendritic cells and regulatory T cells JOURNAL=Frontiers in Immunology VOLUME=15 YEAR=2024 URL=https://www.frontiersin.org/journals/immunology/articles/10.3389/fimmu.2024.1369117 DOI=10.3389/fimmu.2024.1369117 ISSN=1664-3224 ABSTRACT=

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.