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Interleukin-36 gamma previously known as interleukin-1 family member 9 (IL1F9) is a protein that in humans is encoded by the IL36G gene.[1][2][3][4]


The protein encoded by this gene is a member of the interleukin-1 cytokine family. This gene and eight other interleukin-1 family genes form a cytokine gene cluster on chromosome 2.[5] The activity of this cytokine is mediated via the interleukin-1 receptor-like 2 (IL1RL2/IL1R-rp2/IL-36 receptor), and is specifically inhibited by interleukin-36 receptor antagonist, (IL-36RA/IL1F5/IL-1 delta). Interferon-gamma, tumor necrosis factor-alpha and interleukin-1 β (IL-1β) are reported to stimulate the expression of this cytokine in keratinocytes. The expression of this cytokine in keratinocytes can also be induced by a multiple Pathogen-Associated Molecular Patterns (PAMPs).[6] Both IL-36γ mRNA and protein have been linked to psoriasis lesions and has been used as a biomarker for differentiating between eczema and psoriasis.[7][8] As with many other interleukin-1 family cytokines IL-36γ requires proteolytic cleavage of its N-terminus for full biological activity.[9] However, unlike IL-1β the activation of IL-36γ is inflammasome-independent and is specifically cleaved by the protease cathepsin S.[10]


  1. Busfield SJ, Comrack CA, Yu G, Chickering TW, Smutko JS, Zhou H, Leiby KR, Holmgren LM, Gearing DP, Pan Y (June 2000). "Identification and gene organization of three novel members of the IL-1 family on human chromosome 2". Genomics. 66 (2): 213–6. doi:10.1006/geno.2000.6184. PMID 10860666.
  2. Kumar S, McDonnell PC, Lehr R, Tierney L, Tzimas MN, Griswold DE, Capper EA, Tal-Singer R, Wells GI, Doyle ML, Young PR (April 2000). "Identification and initial characterization of four novel members of the interleukin-1 family". The Journal of Biological Chemistry. 275 (14): 10308–14. doi:10.1074/jbc.275.14.10308. PMID 10744718.
  3. Nicklin MJ, Barton JL, Nguyen M, FitzGerald MG, Duff GW, Kornman K (May 2002). "A sequence-based map of the nine genes of the human interleukin-1 cluster". Genomics. 79 (5): 718–25. doi:10.1006/geno.2002.6751. PMID 11991722.
  4. Taylor SL, Renshaw BR, Garka KE, Smith DE, Sims JE (May 2002). "Genomic organization of the interleukin-1 locus". Genomics. 79 (5): 726–33. doi:10.1006/geno.2002.6752. PMID 11991723.
  5. Garlanda C, Dinarello CA, Mantovani A (December 2013). "The interleukin-1 family: back to the future". Immunity. 39 (6): 1003–18. doi:10.1016/j.immuni.2013.11.010. PMC 3933951. PMID 24332029.
  6. Gabay, C; Towne, JE (April 2015). "Regulation and function of interleukin-36 cytokines in homeostasis and pathological conditions". Journal of Leukocyte Biology. 97 (4): 645–52. doi:10.1189/jlb.3RI1014-495R. PMID 25673295.
  7. Berekméri, A; Latzko, A; Alase, A; Macleod, T; Ainscough, JS; Laws, P; Goodfield, M; Wright, A; Helliwell, P; Edward, S; Brown, GD; Reid, DM; Wenzel, J; Stacey, M; Wittmann, M (18 May 2018). "Detection of IL-36y via non-invasive tape stripping reliably discriminates psoriasis from atopic eczema". The Journal of Allergy and Clinical Immunology. doi:10.1016/j.jaci.2018.04.031. hdl:2164/10849. PMID 29782895.
  8. D'Erme AM, Wilsmann-Theis D, Wagenpfeil J, Hölzel M, Ferring-Schmitt S, Sternberg S, Wittmann M, Peters B, Bosio A, Bieber T, Wenzel J (April 2015). "IL-36γ (IL-1F9) is a biomarker for psoriasis skin lesions". The Journal of Investigative Dermatology. 135 (4): 1025–32. doi:10.1038/jid.2014.532. PMID 25525775.
  9. Towne JE, Renshaw BR, Douangpanya J, Lipsky BP, Shen M, Gabel CA, Sims JE (December 2011). "Interleukin-36 (IL-36) ligands require processing for full agonist (IL-36α, IL-36β, and IL-36γ) or antagonist (IL-36Ra) activity". The Journal of Biological Chemistry. 286 (49): 42594–602. doi:10.1074/jbc.M111.267922. PMC 3234937. PMID 21965679.
  10. Ainscough JS, Macleod T, McGonagle D, Brakefield R, Baron JM, Alase A, Wittmann M, Stacey M (March 2017). "Cathepsin S is the major activator of the psoriasis-associated proinflammatory cytokine IL-36γ". Proceedings of the National Academy of Sciences of the United States of America. 114 (13): E2748–E2757. doi:10.1073/pnas.1620954114. PMC 5380102. PMID 28289191.

Further reading

  • Nicklin MJ, Weith A, Duff GW (January 1994). "A physical map of the region encompassing the human interleukin-1 alpha, interleukin-1 beta, and interleukin-1 receptor antagonist genes". Genomics. 19 (2): 382–4. doi:10.1006/geno.1994.1076. PMID 8188271.
  • Nothwang HG, Strahm B, Denich D, Kübler M, Schwabe J, Gingrich JC, Jauch A, Cox A, Nicklin MJ, Kurnit DM, Hildebrandt F (May 1997). "Molecular cloning of the interleukin-1 gene cluster: construction of an integrated YAC/PAC contig and a partial transcriptional map in the region of chromosome 2q13". Genomics. 41 (3): 370–8. doi:10.1006/geno.1997.4654. PMID 9169134.
  • Mulero JJ, Pace AM, Nelken ST, Loeb DB, Correa TR, Drmanac R, Ford JE (October 1999). "IL1HY1: A novel interleukin-1 receptor antagonist gene". Biochemical and Biophysical Research Communications. 263 (3): 702–6. doi:10.1006/bbrc.1999.1440. PMID 10512743.
  • Smith DE, Renshaw BR, Ketchem RR, Kubin M, Garka KE, Sims JE (January 2000). "Four new members expand the interleukin-1 superfamily". The Journal of Biological Chemistry. 275 (2): 1169–75. doi:10.1074/jbc.275.2.1169. PMID 10625660.
  • Barton JL, Herbst R, Bosisio D, Higgins L, Nicklin MJ (November 2000). "A tissue specific IL-1 receptor antagonist homolog from the IL-1 cluster lacks IL-1, IL-1ra, IL-18 and IL-18 antagonist activities". European Journal of Immunology. 30 (11): 3299–308. doi:10.1002/1521-4141(200011)30:11<3299::AID-IMMU3299>3.0.CO;2-S. PMID 11093146.
  • Pan G, Risser P, Mao W, Baldwin DT, Zhong AW, Filvaroff E, Yansura D, Lewis L, Eigenbrot C, Henzel WJ, Vandlen R (January 2001). "IL-1H, an interleukin 1-related protein that binds IL-18 receptor/IL-1Rrp". Cytokine. 13 (1): 1–7. doi:10.1006/cyto.2000.0799. PMID 11145836.
  • Lin H, Ho AS, Haley-Vicente D, Zhang J, Bernal-Fussell J, Pace AM, Hansen D, Schweighofer K, Mize NK, Ford JE (June 2001). "Cloning and characterization of IL-1HY2, a novel interleukin-1 family member". The Journal of Biological Chemistry. 276 (23): 20597–602. doi:10.1074/jbc.M010095200. PMID 11278614.
  • Debets R, Timans JC, Homey B, Zurawski S, Sana TR, Lo S, Wagner J, Edwards G, Clifford T, Menon S, Bazan JF, Kastelein RA (August 2001). "Two novel IL-1 family members, IL-1 delta and IL-1 epsilon, function as an antagonist and agonist of NF-kappa B activation through the orphan IL-1 receptor-related protein 2". Journal of Immunology. 167 (3): 1440–6. doi:10.4049/jimmunol.167.3.1440. PMID 11466363.
  • Sims JE, Nicklin MJ, Bazan JF, Barton JL, Busfield SJ, Ford JE, Kastelein RA, Kumar S, Lin H, Mulero JJ, Pan J, Pan Y, Smith DE, Young PR (October 2001). "A new nomenclature for IL-1-family genes". Trends in Immunology. 22 (10): 536–7. doi:10.1016/S1471-4906(01)02040-3. PMID 11574262.
  • Towne JE, Garka KE, Renshaw BR, Virca GD, Sims JE (April 2004). "Interleukin (IL)-1F6, IL-1F8, and IL-1F9 signal through IL-1Rrp2 and IL-1RAcP to activate the pathway leading to NF-kappaB and MAPKs". The Journal of Biological Chemistry. 279 (14): 13677–88. doi:10.1074/jbc.M400117200. PMID 14734551.
  • Dennis RA, Trappe TA, Simpson P, Carroll C, Huang BE, Nagarajan R, Bearden E, Gurley C, Duff GW, Evans WJ, Kornman K, Peterson CA (November 2004). "Interleukin-1 polymorphisms are associated with the inflammatory response in human muscle to acute resistance exercise". The Journal of Physiology. 560 (Pt 3): 617–26. doi:10.1113/jphysiol.2004.067876. PMC 1665272. PMID 15331687.
  • Vos JB, van Sterkenburg MA, Rabe KF, Schalkwijk J, Hiemstra PS, Datson NA (May 2005). "Transcriptional response of bronchial epithelial cells to Pseudomonas aeruginosa: identification of early mediators of host defense". Physiological Genomics. 21 (3): 324–36. doi:10.1152/physiolgenomics.00289.2004. PMID 15701729.