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The Il-36 pathway plays a key role in the pathogenesis of GPP

THE PATHOLOGY OF GPP

THE IL-36 PATHWAY PLAYS A KEY ROLE IN THE PATHOGENESIS OF GPP1

GPP IS DRIVEN BY THE IL-36 PATHWAY1

IL-36 agonists bind to the IL-36 receptor, or IL-36R, on keratinocyte surfaces, promoting IL-36 expression. This pathway regulates the expression of numerous cytokines, triggering a pro-inflammatory cycle.1,2

IL-36 agonists bind to the IL-36 receptor, or IL-36R.

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THE IL-36 PATHWAY IS REGULATED BY THE INTERPLAY BETWEEN IL-36 AGONISTS AND ANTAGONISTS3,4

Any imbalance between IL-36 agonists and antagonists causes dysregulation in the IL-36 pathway. Unregulated IL-36R signalling leads to uncontrolled induction of downstream inflammatory cytokines, which play a key role in the pathogenesis of GPP.1,2,5

Any imbalance between IL-36 agonists and antagonists causes dysregulation in the IL-36 pathway.

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SEE HOW THE IL-36 PATHWAY WORKS AND LEARN ABOUT ITS ROLE IN THE PATHOGENESIS OF GPP1

The IL-36 pathway is regulated by the interplay between the IL-36 agonists and the antagonist IL-36Ra to ensure a balanced immune response.3,4

GPP=Generalized Pustular Psoriasis; IL=interleukin; IL-1RAcP=interleukin-1 receptor accessory protein; IL-36R=IL-36 receptor; IL-36Ra=interleukin-36 receptor antagonist; TIR=Toll/interleukin-1 receptor.

REFERENCES

  1. Furue K, Yamamura K, Tsuji G, et al. Highlighting interleukin-36 signalling in plaque psoriasis and pustular psoriasis. Acta Derm Venereol. 2018;98(1):5-13. doi:10.2340/00015555-2808 

  2. Marrakchi S, Guigue P, Renshaw BR, et al. Interleukin-36–receptor antagonist deficiency and generalized pustular psoriasis. N Engl J Med. 2011;365(77):620-628. doi:10.1056/NEJMoa1013068

  3. Bassoy EY, Towne JE, Gabay C. Regulation and function of interleukin-36 cytokines. Immunol Rev. 2018;281(1):169-178. doi:10.1111/imr.12610 

  4. Carrier Y, Ma HL, Ramon HE, et al. Inter-regulation of Th17 cytokines and the IL-36 cytokines in vitro and in vivo: implications in psoriasis pathogenesis. J Invest Dermatol. 2011;131(12):2428-2437. doi:10.1038/jid.2011.234 

  5. Gabay C, Towne JE. Regulation and function of interleukin-36 cytokines in homeostasis and pathological conditions. J Leukoc Biol. 2015;97(4):645-652. doi:10.1189/jlb.3RI1014-495R

  6. Kharawala S, Golembesky AK, Bohn RL, Esser D. The clinical, humanistic, and economic burden of generalized pustular psoriasis: a structured review. Expert Rev Clin Immunol. 2020;16(3):239-252. doi:10.1080/1744666X.2019.1708193 

  7. Strober B, Kotowsky N, Medeiros R, et al. Unmet medical needs in the treatment and management of generalized pustular psoriasis flares: evidence from a survey of Corrona registry dermatologists. Dermatol Ther (Heidelb). 2021;11(2):529-541. doi:10.1007/s13555-021-00493-0