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<p>Inducible T-cell costimulator (ICOS) and its ligand ICOSL are members of the CD28 and B7 receptor families that play central roles in immune regulation. While the role of ICOS in T-cell activation and differentiation has been widely studied, increasing evidence indicates that ICOSL, which is broadly expressed across both immune and nonimmune cell types, also functions as a signaling receptor. This review focuses on ICOSL-mediated reverse signaling and its ability to modulate the behavior of ICOSL-expressing immune and stromal cells. In vitro, ICOSL activation induces cell type-specific responses, most notably regulating cell migration. In vivo, ICOSL signaling influences key processes such as tumor growth, bone remodeling, wound healing, liver regeneration, and sepsis. Taken together, these findings expand the conventional view of ICOSL as a passive ligand and suggest that ICOSL is a versatile immune modulator with therapeutic relevance in cancer, inflammatory, and fibrotic diseases.</p>

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ICOSL: more than a trigger of ICOS function

  • 期刊论文

  • 出版模式：

    开放获取

  • 发表日期：

    2025年11月26日

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  • Ian Stoppa,
  • Alessia Provera,
  • Sara Sacchetti,
  • Nausicaa Clemente,
  • Deepika Pantham,
  • Foteini Christaki,
  • Cristina Vecchio,
  • Anteneh Nigussie Sheferaw,
  • Roberta Rolla,
  • Chiara Dianzani,
  • Salvatore Sutti,
  • Umberto Dianzani

摘要

Inducible T-cell costimulator (ICOS) and its ligand ICOSL are members of the CD28 and B7 receptor families that play central roles in immune regulation. While the role of ICOS in T-cell activation and differentiation has been widely studied, increasing evidence indicates that ICOSL, which is broadly expressed across both immune and nonimmune cell types, also functions as a signaling receptor. This review focuses on ICOSL-mediated reverse signaling and its ability to modulate the behavior of ICOSL-expressing immune and stromal cells. In vitro, ICOSL activation induces cell type-specific responses, most notably regulating cell migration. In vivo, ICOSL signaling influences key processes such as tumor growth, bone remodeling, wound healing, liver regeneration, and sepsis. Taken together, these findings expand the conventional view of ICOSL as a passive ligand and suggest that ICOSL is a versatile immune modulator with therapeutic relevance in cancer, inflammatory, and fibrotic diseases.