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A Simple and Efficient Method for Testing Immunomodulatory Agents for Generation of Tolerogenic Dendritic Cells from Human CD14+ Monocytes
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A Simple and Efficient Method for Testing Immunomodulatory Agents for Generation of Tolerogenic Dendritic Cells from Human CD14+ Monocytes

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Bispecific antibodies tethering innate receptors induce human tolerant-dendritic cells and regulatory T cells

Lucille Lamendour1, Mäelle Gilotin1, Nora Deluce-Kakwata Nkor1

  • 1EA7501, Groupe Innovation et Ciblage Cellulaire, Team Fc Récepteurs, Anticorps et MicroEnvironnement (FRAME), Université de Tours, Tours, France.

Frontiers in Immunology
|April 11, 2024
PubMed

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-β1TLR2bispecific antibodyhuman dendritic cellinnate receptorsinterleukine-10tolerant dendritic celltype C lectin

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