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Article Dans Une Revue Frontiers in Immunology Année : 2024

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

Mäelle Gilotin
  • Fonction : co premier-auteur
Zineb Lakhrif
Daniel Meley
  • Fonction : Auteur
Anne Di Tommaso
Jean-Jacques Pin
  • Fonction : Auteur
  • PersonId : 905079
Nicolas Aubrey

Résumé

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.
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hal-04601179 , version 1 (04-06-2024)

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Lucille Lamendour, Mäelle Gilotin, Nora Deluce-Kakwata Nkor, Zineb Lakhrif, Daniel Meley, et al.. Bispecific antibodies tethering innate receptors induce human tolerant-dendritic cells and regulatory T cells. Frontiers in Immunology, 2024, 15, pp.1369117. ⟨10.3389/fimmu.2024.1369117⟩. ⟨hal-04601179⟩
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