A Secreted Immune Checkpoint - IL-18BP

Interleukin 18 binding protein (IL-18BP) is a protein that plays a role in the immune system. It is involved in the regulation of interleukin 18 (IL-18) activity, which contributes to the fine-tuning of the immune system and helps maintain immune homeostasis.

The concept of IL-18BP as a secretory immune checkpoint has been explored in scientific studies. It has the potential to serve as a target for therapeutic intervention in situations where modulation of the immune response is required. Creative Biolabs explores the biological properties of IL-18BP and its significance in immune regulation.

Introduction to IL-18BP

Fig. 1 Schematic of IL-18 signaling.¹

IL-18 is produced by a variety of cell types, including macrophages, dendritic cells, and epithelial cells, and is involved in the regulation of innate and adaptive immune responses. IL-18 acts by binding to its receptor complex, which consists of IL-18Rα and IL-18Rβ, thereby activating downstream signaling pathways.

IL-18BP is a secreted protein and a natural antagonist of the pro-inflammatory cytokine IL-18. IL-18BP acts as a decoy receptor for IL-18 and competes with IL-18Rα for binding to IL-18. By sequestering IL-18 and preventing its interaction with its receptor complex, IL-18BP effectively inhibits IL-18 signaling and suppresses immune responses.

This regulatory mechanism allows IL-18BP to fine-tune the immune system to prevent excessive inflammation while maintaining the ability to mount an appropriate immune response.

Regulation of IL-18BP Expression

IL-18BP expression is tightly regulated and can be modulated by a number of factors.

• One such factor is the presence of other cytokines and inflammatory mediators. For example, IL-12 has been shown to upregulate IL-18BP expression, suggesting that IL-12 may counterbalance the pro-inflammatory effects of IL-18 by promoting IL-18BP production.
• Several transcription factors have been implicated in the regulation of IL-18BP expression.
  • Nuclear factor-κB (NF-κB) has been shown to bind to the promoter region of the IL-18BP gene and activate its transcription.
  • Interferon regulatory factor 1 (IRF1) and signal transducer and activator of transcription 1 (STAT1), have also been found to regulate IL-18BP expression in response to different stimuli.

Biological Functions of IL-18BP

IL-18BP is associated with a variety of physiologic and pathologic processes.

• In infectious diseases, IL-18BP can limit excessive inflammation and tissue damage caused by overactive immune responses.
• In autoimmune diseases, where the immune system mistakenly attacks its own tissues, IL-18BP may play a role in suppressing the autoimmune response.
• IL-18BP has been shown to modulate allergic responses by inhibiting the production of Th2 cytokines associated with allergic inflammation.

The discovery of IL-18BP as a secretory immune checkpoint has opened up new possibilities for therapeutic intervention in various diseases. Manipulation of IL-18BP activity could potentially be used to enhance or suppress immune responses.

IL-18BP represents an exciting new addition to the growing list of immune checkpoints involved in immune regulation. At Creative Biolabs, we are at the forefront of these advances, working to explore new immune checkpoints.

Reference

1. Mühl Heiko and Malte Bachmann. "IL-18/IL-18BP and IL-22/IL-22BP: two interrelated couples with therapeutic potential." Cellular signalling 63 (2019): 109388.

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