IL36RN Human, His
Description
Overview of IL36RN Human, His
IL36RN Human, His refers to a recombinant human interleukin-36 receptor antagonist (IL-36Ra) protein engineered with a histidine (His) tag for purification and solubility. This protein belongs to the interleukin-1 (IL-1) cytokine family and plays a critical role in regulating inflammation by antagonizing IL-36 cytokines (IL-36α, IL-36β, IL-36γ). Its deficiency is linked to severe inflammatory skin disorders, including generalized pustular psoriasis (GPP) and acute generalized exanthematous pustulosis (AGEP) .
Mechanism of Action
IL-36Ra competitively inhibits IL-36 cytokine binding to their receptor complex (IL-36R/IL1RL2 and IL1RAP), preventing downstream pro-inflammatory signaling . In healthy individuals, this regulation maintains homeostasis, while mutations in IL36RN disrupt this balance, leading to uncontrolled inflammation .
Wound Healing and Inflammation
Studies in Il36rn−/− mice revealed delayed wound healing due to:
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Increased Neutrophil/Macrophage Infiltration: Enhanced CXCL1 and IL-36γ expression .
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Cytokine Dysregulation: Elevated TGF-β and IL-36γ at early wound stages .
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TLR4 Dependency: TLR4 inhibitor (TAK-242) restored normal healing, indicating IL-36Ra modulates TLR4-mediated inflammation .
Disease Association
Key Mutation: The L27P mutation disrupts IL-36Ra stability and receptor binding, causing defective cytokine inhibition .
Experimental Uses
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Inflammatory Pathway Studies: Investigating IL-36/TLR4 crosstalk in skin diseases .
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Drug Development: Screening inhibitors of IL-36R or TLR4 for psoriasis/AGEP therapies .
Therapeutic Potential
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IL-36Ra Replacement: Restoring IL-36Ra function in IL36RN-deficient patients .
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Cytokine Modulation: Targeting IL-36γ or CXCL1 to reduce neutrophil recruitment .
References
Product Specs
Product Science Overview
Interleukin-36 Receptor Antagonist (IL-36Ra) is a member of the interleukin-36 family of cytokines, which also includes three agonists: interleukin-36 alpha, interleukin-36 beta, and interleukin-36 gamma. These cytokines are part of the larger interleukin-1 superfamily . The primary function of IL-36Ra is to inhibit the pro-inflammatory effects of the interleukin-36 cytokines by competing with their receptor, interleukin-36 receptor (IL-36R), thereby preventing the recruitment of the accessory protein interleukin-1 receptor accessory protein (IL-1RAcP) .
IL-36Ra is a protein coding gene known as IL36RN. It is expressed in various tissues, including the skin, lungs, intestines, joints, and brain . The receptor activation follows a two-step mechanism: the agonist first binds to IL-36R, forming a binary complex that recruits IL-1RAcP. This assembled ternary complex brings together intracellular Toll/Interleukin-1 receptor (TIR) domains of receptors, which activate downstream nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) and mitogen-activated protein kinase (MAPK) signaling .
Mutations in the IL36RN gene can lead to a decrease or production of defective IL-36Ra protein, which has been associated with several inflammatory skin diseases, including generalized pustular psoriasis, acrodermatitis continua suppurativa Hallopeau, and acute generalized exanthematous pustulosis . Dysregulation of IL-36Ra can stimulate keratinocyte and immune cells, enhancing the T-helper 17/T-helper 23 axis and inducing psoriatic-like skin disorders .
Recombinant IL-36Ra, particularly the human recombinant form with a His tag, is produced using recombinant DNA technology. The His tag is a sequence of histidine residues added to the protein to facilitate purification through affinity chromatography. This recombinant form is used in research to study the protein’s function, signaling pathways, and potential therapeutic applications.
