Elucidating the Roles of lL-1Rll in the Regulation of Human Immune System

Interleukin-1 (IL-1) family of cytokines plays a critical role in the regulation of the human immune responses. These family ligands include 11 members with three different types of functions, agonist activity, receptor antagonists, and an anti-inflammatory cytokine [1,2]. Extracellular signaling mechanisms in this family activates through the binding of ligands to their specific receptors on the cell surface. These receptors are known as Interleukin-1 Receptors (IL-1Rs) [3,4]. Interleukin-1 Receptor type II (IL-1RII) is a non- signaling receptor of the IL-1 receptors family. It is homologous to the signaling receptor of IL-1 receptor (IL-1RI) in its extracellular region. Both receptors can bind to IL-1β, an agonist member of the IL-1 family cytokines, with high affinity [5]. Also, they bind the same IL-1 Receptor Accessory Protein (IL-1RAcP) to obtain their functional complexes. Despite their similarity, IL-1RII is unable to form a transmembrane receptor complex like IL-1RI because of lacking intracellular Toll Interleukin Receptor (TIR) domain. Consequently, after ligand binding, it will inhibit IL-1 βs activation. For this reason, it is Known as a decoy receptor of the IL-1 receptor family [4,5]. (Figure1 shows the mechanism of IL-1RII complex). Furthermore, glycosylation has significant effects on the dynamics and conformation of protein structures [6]. Previous studies have shown the importance of glycans in the receptors folding and their ligand binding [6,7,8]. Based on the glycan type and its linkage to protein, different classes of glycosylation exist, including N-Linked and O-Linked glycosylation [6]. The latest simulations of the N-glycosylation of the IL-1RI have demonstrated a critical aspect of this attachment on the dynamics, conformation, and ligands binding of IL-1RI[7]. Putting together, these findings clarify the value of investigating the structural role of glycosylation in the dynamics and conformation of the IL-1RII that was carried out in this study. Also, understanding these details is required to deeply realize the IL-1RII activation mechanism and regulation of the immune responses.