Ex vivo-expanded human CD19 + TIM-1 + regulatory B cells suppress immune responses in vivo and are dependent upon the TIM-1/STAT3 axis.

Autor: Shankar S; Translational Research and Immunology Group, Nuffield Department of Surgical Sciences, University of Oxford, Oxford, UK. sushma.shankar@nds.ox.ac.uk.; Oxford Transplant Centre, Nuffield Department of Surgical Sciences, University of Oxford, Oxford, UK. sushma.shankar@nds.ox.ac.uk., Stolp J; Translational Research and Immunology Group, Nuffield Department of Surgical Sciences, University of Oxford, Oxford, UK., Juvet SC; Translational Research and Immunology Group, Nuffield Department of Surgical Sciences, University of Oxford, Oxford, UK., Beckett J; Translational Research and Immunology Group, Nuffield Department of Surgical Sciences, University of Oxford, Oxford, UK., Macklin PS; Nuffield Department of Medicine Research Building, Nuffield Department of Medicine, University of Oxford, Oxford, UK., Issa F; Translational Research and Immunology Group, Nuffield Department of Surgical Sciences, University of Oxford, Oxford, UK., Hester J; Translational Research and Immunology Group, Nuffield Department of Surgical Sciences, University of Oxford, Oxford, UK., Wood KJ; Translational Research and Immunology Group, Nuffield Department of Surgical Sciences, University of Oxford, Oxford, UK. kathryn.wood@nds.ox.ac.uk.
Jazyk: angličtina
Zdroj: Nature communications [Nat Commun] 2022 Jun 03; Vol. 13 (1), pp. 3121. Date of Electronic Publication: 2022 Jun 03.
DOI: 10.1038/s41467-022-30613-z
Abstrakt: Regulatory B cells (Breg) are a heterogenous population with immune-modulating functions. The rarity of human IL-10 + Breg makes translational studies difficult. Here we report ex vivo expansion of human B cells with in vivo regulatory function (expBreg). CD154-stimulation of human CD19 + B cells drives >900-fold expansion of IL-10 + B cells that is maintained in culture for 14 days. Whilst expBreg-mediated suppressive function is partially dependent on IL-10 expression, CRISPR-mediated gene deletions demonstrate predominant roles for TIM-1 and CD154. TIM-1 regulates STAT3 signalling and modulates downstream suppressive function. In a clinically relevant humanised mouse model of skin transplantation, expBreg prolongs human allograft survival. Meanwhile, CD19 + CD73 - CD25 + CD71 + TIM-1 + CD154 + Breg cells are enriched in the peripheral blood of human donors with cutaneous squamous cell carcinoma (SCC). TIM-1 + and pSTAT3 + B cells are also identified in B cell clusters within histological sections of human cutaneous SCC tumours. Our findings thus provide insights on Breg homoeostasis and present possible targets for Breg-related therapies.
(© 2022. The Author(s).)
Databáze: MEDLINE
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