ICOSL: more than a trigger of ICOS function

Area of Science:

• Immunology
• Cell Biology
• Molecular Medicine

Background:

• Inducible T-cell costimulator (ICOS) and its ligand (ICOSL) are key regulators in immune responses.
• While ICOS function is well-researched, ICOSL's role as a signaling receptor is increasingly recognized.
• ICOSL is expressed broadly in immune and non-immune cells.

Purpose of the Study:

• To review the emerging evidence for ICOSL-mediated reverse signaling.
• To explore how ICOSL signaling modulates the behavior of ICOSL-expressing cells.
• To highlight the physiological and therapeutic implications of ICOSL reverse signaling.

Main Methods:

• Literature review of studies investigating ICOSL reverse signaling.
• Analysis of in vitro and in vivo experimental data.
• Synthesis of findings on ICOSL's impact on cellular behavior and physiological processes.

Main Results:

• In vitro ICOSL activation elicits cell type-specific responses, notably affecting cell migration.
• In vivo ICOSL signaling impacts tumor growth, bone remodeling, wound healing, liver regeneration, and sepsis.
• ICOSL functions as a versatile modulator beyond its role as a passive ligand.

Conclusions:

• ICOSL reverse signaling significantly influences immune and stromal cell behavior.
• ICOSL is a crucial modulator in various physiological and pathological conditions.
• Targeting ICOSL reverse signaling presents therapeutic opportunities for cancer, inflammatory, and fibrotic diseases.