- Guide to PHARMACOLOGY
Synonyms: IL-1 related protein 3 (IL1RP3) | IL-1F5 | IL-36ra | IL1F5 | interleukin 1 family member 5 (delta)
Compound class: Endogenous peptide in human, mouse or rat
Comment: IL-36 receptor antagonist is also known as IL-36RA or IL36RN, the latter being the gene symbol. It acts by antagonising the binding of IL-36α, β and γ to interleukin 1 receptor like 2 (IL1RL2) which is the ligand binding component of the functional IL-36 receptor.
Abnormailites in the IL36RN gene that produce mutated IL-36RA protein structures with compromised function have been identified as a cause of unregulated inflammatory cytokine secretion which drives the repeated inflammatory episodes that characterise the life-threatening condition, generalized pustular psoriasis [4-5]. Where abnormal IL-36RA underlies generalized pustular psoriasis the condition can be referred to as DITRA (deficiency of interleukin 36 antagonist). DITRA has been identified as the cause of other pustular phenotypes, that have emerged as variants of pustular psoriasis [1,4,7]. An antibody that mimics IL-36RA's antagonist activity at the IL-36 receptor (MAB92) has been described . MAB92 inhibits proinflammatory cytokine production in primary human keratinocytes and dermal fibroblasts in vitro.
1. Abbas O, Itani S, Ghosn S, Kibbi AG, Fidawi G, Farooq M, Shimomura Y, Kurban M. (2013)
Acrodermatitis continua of Hallopeau is a clinical phenotype of DITRA: evidence that it is a variant of pustular psoriasis.
Dermatology (Basel), 226 (1): 28-31. [PMID:23428889]
2. Ganesan R, Raymond EL, Mennerich D, Woska Jr JR, Caviness G, Grimaldi C, Ahlberg J, Perez R, Roberts S, Yang D et al.. (2017)
Generation and functional characterization of anti-human and anti-mouse IL-36R antagonist monoclonal antibodies.
MAbs, 9 (7): 1143-1154. [PMID:28726542]
3. Gresnigt MS, van de Veerdonk FL. (2013)
Biology of IL-36 cytokines and their role in disease.
Semin Immunol, 25 (6): 458-65. [PMID:24355486]
4. Kanazawa N, Nakamura T, Mikita N, Furukawa F. (2013)
Novel IL36RN mutation in a Japanese case of early onset generalized pustular psoriasis.
J Dermatol, 40 (9): 749-51. [PMID:23834760]
5. Marrakchi S, Guigue P, Renshaw BR, Puel A, Pei XY, Fraitag S, Zribi J, Bal E, Cluzeau C, Chrabieh M et al.. (2011)
Interleukin-36-receptor antagonist deficiency and generalized pustular psoriasis.
N Engl J Med, 365 (7): 620-8. [PMID:21848462]
6. Mulero JJ, Pace AM, Nelken ST, Loeb DB, Correa TR, Drmanac R, Ford JE. (1999)
IL1HY1: A novel interleukin-1 receptor antagonist gene.
Biochem Biophys Res Commun, 263 (3): 702-6. [PMID:10512743]
7. Tauber M, Bal E, Pei XY, Madrange M, Khelil A, Sahel H, Zenati A, Makrelouf M, Boubridaa K, Chiali A et al.. (2016)
IL36RN Mutations Affect Protein Expression and Function: A Basis for Genotype-Phenotype Correlation in Pustular Diseases.
J Invest Dermatol, 136 (9): 1811-9. [PMID:27220475]