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target has curated data in GtoImmuPdb
Target id: 1907
Nomenclature: Interleukin-36 receptor
| Quaternary Structure: Subunits |
| Interleukin-1 receptor-like 2 (Ligand-binding subunit) |
| IL-1 receptor accessory protein (Other subunit) |
Natural/Endogenous Ligands  |
| IL-36α {Sp: Human} |
| IL-36β {Sp: Human} |
| IL-36γ {Sp: Human} |
| IL-36 receptor antagonist {Sp: Human} |
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| Immunopharmacology Comments |
| The functional IL-36 receptor is a heterodimer containing interleukin-1 receptor-like 2 (IL1RL2) as the ligand binding moeity and the IL-1 receptor accessory protein (IL1RAP). The cytokines IL-36α, IL-36β and IL-36γ are agonists of the IL-36 receptor. Activation by these agonists is opposed by the IL-36 receptor antagonist (IL-36RA) cytokine. The normal biological functions of IL-36 cytokines and their roles in pathological conditions are reviewed by Gabay and Towne (2015) [2]. The IL-36 cytokines are being investigated as novel targets for inflammatory diseases- reviewed by Walsh and Fallon (2016) [5]. Of note is the implication of the IL-36 system in psoriatic skin inflammation [1,4]. Recent work by Liu et al. (2017) has shown that IL-36R/MyD88 signaling is the critical primary driver of IL-17A production in inflamed skin and for the generation of IL-17A-producing T cells in the draining lymph nodes (in mouse models of S. aureus-induced epithelial inflammation) [3], work that recapitulates the role of the IL-36/IL-36R signalling pathway in epidermal skin inflammation, and adds more evidence supporting this pathway as a new druggable target for atopic dermatitis. |
| Tissue Distribution Comments | |
| Expression of IL-36R is restricted to epithelial cells in direct contact with the environment, including the skin. |
1. Frey S, Derer A, Messbacher ME, Baeten DL, Bugatti S, Montecucco C, Schett G, Hueber AJ. (2013) The novel cytokine interleukin-36α is expressed in psoriatic and rheumatoid arthritis synovium. Ann Rheum Dis, 72 (9): 1569-74. [PMID:23268368]
2. Gabay C, Towne JE. (2015) Regulation and function of interleukin-36 cytokines in homeostasis and pathological conditions. J Leukoc Biol, 97 (4): 645-52. [PMID:25673295]
3. Liu H, Archer NK, Dillen CA, Wang Y, Ashbaugh AG, Ortines RV, Kao T, Lee SK, Cai SS, Miller RJ et al.. (2017) Staphylococcus aureus Epicutaneous Exposure Drives Skin Inflammation via IL-36-Mediated T Cell Responses. Cell Host Microbe, 22 (5): 653-666.e5. [PMID:29120743]
4. Mahil SK, Catapano M, Di Meglio P, Dand N, Ahlfors H, Carr IM, Smith CH, Trembath RC, Peakman M, Wright J et al.. (2017) An analysis of IL-36 signature genes and individuals with IL1RL2 knockout mutations validates IL-36 as a psoriasis therapeutic target. Sci Transl Med, 9 (411). [PMID:29021166]
5. Walsh PT, Fallon PG. (2018) The emergence of the IL-36 cytokine family as novel targets for inflammatory diseases. Ann N Y Acad Sci, 1417 (1): 23-34. [PMID:27783881]
Immunoglobulin-like family of IL-1 receptors: Interleukin-36 receptor. Last modified on 10/07/2018. Accessed on 16/04/2024. IUPHAR/BPS Guide to PHARMACOLOGY, https://www.guidetopharmacology.org/GRAC/ObjectDisplayForward?objectId=1907.
