ICOSL Stimulation by ICOS-Fc Accelerates Cutaneous Wound Healing In Vivo.
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ABSTRACT: Background
ICOS and its ligand ICOSL are immune receptors whose interaction triggers bidirectional signals that modulate the immune response and tissue repair.Aim
The aim of this study was to assess the in vivo effects of ICOSL triggering by ICOS-Fc, a recombinant soluble form of ICOS, on skin wound healing.Methods
The effect of human ICOS-Fc on wound healing was assessed, in vitro, and, in vivo, by skin wound healing assay using ICOS-/- and ICOSL-/- knockout (KO) mice and NOD-SCID-IL2R null (NSG) mice.Results
We show that, in wild type mice, treatment with ICOS-Fc improves wound healing, promotes angiogenesis, preceded by upregulation of IL-6 and VEGF expression; increases the number of fibroblasts and T cells, whereas it reduces that of neutrophils; and increases the number of M2 vs. M1 macrophages. Fittingly, ICOS-Fc enhanced M2 macrophage migration, while it hampered that of M1 macrophages. ICOS-/- and ICOSL-/- KO, and NSG mice showed delayed wound healing, and treatment with ICOS-Fc improved wound closure in ICOS-/- and NSG mice.Conclusion
These data show that the ICOS/ICOSL network cooperates in tissue repair, and that triggering of ICOSL by ICOS-Fc improves cutaneous wound healing by increasing angiogenesis and recruitment of reparative macrophages.
SUBMITTER: Stoppa I
PROVIDER: S-EPMC9266942 | biostudies-literature |
REPOSITORIES: biostudies-literature
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