ICOSL Stimulation by ICOS-Fc Accelerates Cutaneous Wound Healing In Vivo

• Published in: International journal of molecular sciences Vol. 23; no. 13; p. 7363
• Main Authors: Stoppa, Ian, Gigliotti, Casimiro Luca, Clemente, Nausicaa, Pantham, Deepika, Dianzani, Chiara, Monge, Chiara, Puricelli, Chiara, Rolla, Roberta, Sutti, Salvatore, Renò, Filippo, Boldorini, Renzo, Boggio, Elena, Dianzani, Umberto
• Format: Journal Article
• Language: English
• Published: Basel MDPI AG 01.07.2022; MDPI
• Subjects: Angiogenesis; Antigens; Cell adhesion & migration; Cytokines; Fibroblasts; Gene expression; ICOS:ICOSL system; Immune system; In vivo methods and tests; Interleukin 2 receptors; Interleukin 6; Leukocytes (neutrophilic); Lymphocytes; Lymphocytes T; Macrophages; Recruitment; Repair; reparative macrophages; Vascular endothelial growth factor; Wound healing
• ISSN: 1422-0067; 1661-6596; 1422-0067
• DOI: 10.3390/ijms23137363

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.