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.
ICOSL Stimulation by ICOS-Fc Accelerates Cutaneous Wound Healing In Vivo / I. Stoppa, C.L. Gigliotti, N. Clemente, D. Pantham, C. Dianzani, C. Monge, C. Puricelli, R. Rolla, S. Sutti, F. Reno', R. Boldorini, E. Boggio, U. Dianzani. - In: INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES. - ISSN 1422-0067. - 23:13(2022 Jul), pp. 7363.1-7363.12. [10.3390/ijms23137363]
ICOSL Stimulation by ICOS-Fc Accelerates Cutaneous Wound Healing In Vivo
F. Reno';
2022
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.File | Dimensione | Formato | |
---|---|---|---|
ICOS-Fc wound-healing.pdf
accesso aperto
Dimensione
3.13 MB
Formato
Adobe PDF
|
3.13 MB | Adobe PDF | Visualizza/Apri |
Pubblicazioni consigliate
I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.