N-3-(oxododecanoyl)-L-homoserine lactone promotes the induction of regulatory T-cells by preventing human dendritic cell maturation

Experimental Biology and Medicine
Youqiang LiJianping Liu

Abstract

N-3-(Oxododecanoyl)-L-homoserine lactone (C12) is a small bacterial signaling molecule secreted by Pseudomonas aeruginosa (PA), which activates mammalian cells through TLR4-independent mechanisms. C12 acts as an immunosuppressant and it has been shown to modulate murine bone marrow-derived dendritic cell-mediated T-helper 2 (Th2) cell polarizations in vitro. In the present study, we initially examined the impact of C12 on the maturation of human monocyte-derived dendritic cells (Mo-DCs) and the induction of regulatory T-cells (iTregs) in culture. Our findings demonstrate that C12-treated Mo-DCs failed to undergo lipopolysaccharide (LPS)-induced maturation. At the molecular level, C12 blocked the upregulation of surface molecules, including CD11c, HLA-DR, CD40, and CD80, and it switched to an interleukin (IL)-10(high), IL-12p70(low) phenotype. Moreover, C12 selectively inhibited the capacity of Mo-DCs to stimulate the proliferation of allogeneic CD4(+) T-cells. Otherwise, the C12-treated Mo-DCs promoted the generation of CD4(+)CD25(+)Foxp3(+)-induced regulatory T-cells (iTregs) and enhanced their IL-10 and transforming growth factor (TGF)-β production associated with reduced interferon (IFN)-γ and IL-12p70 production. These find...Continue Reading

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Citations

Oct 18, 2019·The Journal of Immunology : Official Journal of the American Association of Immunologists·Wolfgang VivasOliver Kurzai
Sep 29, 2020·Frontiers in Immunology·Garance CoquantPhilippe Seksik

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Methods Mentioned

BETA
flow cytometry
ELISA

Software Mentioned

Bio
Cell Quest
Linx

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