IL-36 is a member of the IL-1 superfamily and consists of three agonists and one receptor antagonist (IL-36Ra). The three endogenous agonists, IL-36α, –β, and –γ, act primarily as proinflammatory cytokines, and their signaling through the IL-36 receptor (IL-36R) promotes immune cell infiltration and secretion of inflammatory and chemotactic molecules. However, IL-36 signaling also fosters secretion of profibrotic soluble mediators, suggesting a role in fibrotic disorders. IL-36 isoforms and IL-36 have been implicated in inflammatory diseases including psoriasis, arthritis, inflammatory bowel diseases, and allergic rhinitis. Moreover, IL-36 has been connected to fibrotic disorders affecting the kidney, lung, and intestines. This review summarizes the expression, cellular source, and function of IL-36 in inflammation and fibrosis in various organs, and proposes that IL-36 modulation may prove valuable in preventing or treating inflammatory and fibrotic diseases and may reveal a mechanistic link between inflammation and fibrosis.
Michael Elias, Shuai Zhao, Hongnga T. Le, Jie Wang, Markus F. Neurath, Clemens Neufert, Claudio Fiocchi, Florian Rieder
Title and authors | Publication | Year |
---|---|---|
Analysis of Predefined Safety Events Across Spesolimab Trials in Dermatological and Non-Dermatological Conditions
Gordon KB, Tada Y, Anadkat MJ, Choon SE, Elewski B, Barker JN, Mostaghimi A, Eyerich K, Tang M, Haeufel T, Thoma C, Thaçi D |
Dermatology and Therapy | 2025 |
Discovery of selective low molecular weight interleukin-36 receptor antagonists by encoded library technologies
Velcicky J, Cremosnik G, Scheufler C, Meier P, Wirth E, Felber R, Ramage P, Schaefer M, Kaiser C, Lehmann S, Kutil R, Singeisen S, Mueller-Ristig D, Popp S, Cebe R, Lehr P, Kaupmann K, Erbel P, Röhn TA, Giovannoni J, Dumelin CE, Martiny-Baron G |
Nature Communications | 2025 |
Skin‐Protective Performance of Alternative Stratum Corneum Formed by a Pseudo‐Ceramide‐Containing Steroid Lamellar Cream
Yokota M, Matsumoto T, Kawamoto A, Dojo K, Toyama S, Moniaga CS, Ishikawa J, Murase D, Ota N, Tominaga M, Takamori K |
Experimental Dermatology | 2025 |
Inflammation-fibrosis interplay in inflammatory bowel disease: mechanisms, progression, and therapeutic strategies
Li Y, Xu F, Fang Y, Cui Y, Zhu Z, Wu Y, Tong Y, Hu J, Zhu L, Shen H |
Frontiers in Pharmacology | 2025 |
Enhanced IL36RN Expression and Its Association With Immune Microenvironment Predicts Poor Prognosis in Gastric Cancer.
Zhang X, Jiang S, Yin H, Zhang H, Yang L, Sun P, Kuai X, Chen C, Huang J |
Cancer medicine | 2025 |
Increased IL- 36γ in visceral adipose tissue as a key mediator of obesity-driven inflammation in colon cancer
Frühbeck G, Criado S, Gómez-Ambrosi J, Ramírez B, Becerril S, Rodríguez A, Neira G, Salmón-Gómez L, Valentí V, Moncada R, Baixauli J, Silva C, Catalán V |
Journal of Molecular Medicine (Berlin, Germany) | 2025 |
Neutrophil extracellular traps and neutrophilic dermatosis: an update review
Li S, Ying S, Wang Y, Lv Y, Qiao J, Fang H |
Cell Death Discovery | 2024 |
Different expression levels of interleukin-36 in asthma phenotypes.
Li J, Wang Z, Dong H, Hao Y, Gao P, Li W |
Allergy, asthma, and clinical immunology : official journal of the Canadian Society of Allergy and Clinical Immunology | 2024 |
Strategies for targeting cytokines in inflammatory bowel disease.
Neurath MF |
Nature reviews. Immunology | 2024 |
Generalized Pustular Psoriasis and Systemic Organ Dysfunctions
Teshima R, Saito-Sasaki N, Sawada Y |
International journal of molecular sciences | 2024 |
Inflammation accelerating intestinal fibrosis: from mechanism to clinic
Xin S, Liu X, He C, Gao H, Wang B, Hua R, Gao L, Shang H, Sun F, Xu J |
European Journal of Medical Research | 2024 |
Spesolimab in the Management of Generalized Pustular Psoriasis With Concurrent Bullous Pemphigoid and Psoriasis
Teshima R, Saito-Sasaki N, Hitaka T, Sawada Y |
Cureus | 2024 |
Cytokines assets in PLWH in two-drug dolutergravir based or three-drug antiretroviral regimen
Falasca K, Ucciferri C, Di Gasbarro A, Borrelli P, Di Nicola M, Frisenda C, Costantini E, Aielli L, Reale M, Vecchiet J |
BMC Infectious Diseases | 2024 |
Single-cell mass cytometry in immunological skin diseases
Zhao M, Cheng Y, Gao J, Zhou F |
Frontiers in immunology | 2024 |
Biologics as a novel treatment option for palmoplantar pustulosis: a comprehensive review
Leong HF, Wang WH, Peng F |
2024 | |
IL36G-producing neutrophil-like monocytes promote cachexia in cancer.
Hayashi Y, Kamimura-Aoyagi Y, Nishikawa S, Noka R, Iwata R, Iwabuchi A, Watanabe Y, Matsunuma N, Yuki K, Kobayashi H, Harada Y, Harada H |
Nature communications | 2024 |
Patients with hidradenitis suppurativa are associated with risk of new-onset glaucoma: a propensity-score-matched cohort study.
Li CP, Lin CY, Lu HY, Chen SN, Tsai RY, Chang HC, Chen SJ, Gau SY |
International journal of medical sciences | 2024 |
Combined inhibition of IL-1, IL-33 and IL-36 signalling by targeting IL1RAP ameliorates skin and lung fibrosis in preclinical models of systemic sclerosis
Grönberg C, Rattik S, Tran-Manh C, Zhou X, Rius Rigau A, Li YN, Györfi AH, Dickel N, Kunz M, Kreuter A, Matei EA, Zhu H, Skoog P, Liberg D, Distler JH, Trinh-Minh T |
Annals of the Rheumatic Diseases | 2024 |
Sprayable inflammasome-inhibiting lipid nanorods in a polymeric scaffold for psoriasis therapy
Surve D, Fish A, Debnath M, Pinjari A, Lorenzana A, Piya S, Peyton S, Kulkarni A |
Nature Communications | 2024 |
Dual blockade of IL-17A and IL-36 pathways via a bispecific antibody exhibits enhanced anti-inflammatory potency
Ma X, Zhang S, Ren X, Feng Y, Li H, Chen S, Xu J, Wang Y, Peng GY, Yan Q, Jia H, Xia S, Cui X, Chen X, Pan X, Wang S, Yu H, Wei X, Li M, Liu B, Xu J, Qian Q, Zhu X, Zhan Y, Lu L |
Frontiers in Immunology | 2024 |
Advances in understanding the role of interleukins in pulmonary fibrosis (Review)
He Y, Shen X, Zhai K, Nian S |
Experimental and Therapeutic Medicine | 2024 |
Bridging the gap: Integrating exercise mimicry into chronic disease management through suppressing chronic inflammation
Nasb M, Li F, Dayoub L, Wu T, Wei M, Chen N |
Journal of Advanced Research | 2024 |
Targeting the STAT3/IL-36G signaling pathway can be a promising approach to treat rosacea
Meng X, Zhong Y, Kuang X, Zhang Y, Yang L, Cai Y, Wang F, He F, Xie H, Wang B, Li J |
Journal of Advanced Research | 2024 |
Autonomous IL-36R signaling reprograms neutrophils into potent anti-tumor effectors cells
Sumedha Roy, Karen Fitzgerald, Almin Lalani, Chin-wen Lai, Aeryon Kim, Jennie Kim, Peiqi ou, Annie Mirsoian, Xian Liu, Ambika Ramrakhiani, Huiren Zhao, Hong Zhou, Hoada Xu, Hans Meisen, Chi-Ming Li, Bryan Vander Lugt, Steve Thibault, Christine E Tinberg, Jason DeVoss, Jackson Egen, Lawren Wu, Rajkumar Noubade |
Journal of Clinical Investigation | 2023 |
Targeting IL-36 in Inflammatory Skin Diseases.
Fukaura R, Akiyama M |
BioDrugs : clinical immunotherapeutics, biopharmaceuticals and gene therapy | 2023 |
Transcriptomic Differentiation of Phenotypes in Chronic Rhinosinusitis and Its Implications for Understanding the Underlying Mechanisms
Urbančič J, Košak Soklič T, Demšar Luzar A, Hočevar Boltežar I, Korošec P, Rijavec M |
International journal of molecular sciences | 2023 |
Cellular and Molecular Mechanisms of Intestinal Fibrosis
Wu X, Lin X, Tan J, Liu Z, He J, Hu F, Wang Y, Chen M, Liu F, Mao R |
Gut and Liver | 2023 |
Fibro-Stenosing Crohn’s Disease: What Is New and What Is Next?
Solitano V, Dal Buono A, Gabbiadini R, Wozny M, Repici A, Spinelli A, Vetrano S, Armuzzi A |
Journal of Clinical Medicine | 2023 |
New insights on IL‑36 in intestinal inflammation and colorectal cancer (Review)
Li M, Jiang W, Wang Z, Lu Y, Zhang J |
Experimental and therapeutic medicine | 2023 |
Interleukin 36 receptor-inducible matrix metalloproteinase 13 mediates intestinal fibrosis
Koop K, Enderle K, Hillmann M, Ruspeckhofer L, Vieth M, Sturm G, Trajanoski Z, Kühl AA, Atreya R, Leppkes M, Baum P, Roy J, Martin A, Neurath MF, Neufert C |
Frontiers in immunology | 2023 |
The Role of Genetic and Epigenetic Regulation in Intestinal Fibrosis in Inflammatory Bowel Disease: A Descending Process or a Programmed Consequence?
Jarmakiewicz-Czaja S, Sokal A, Ferenc K, Motyka E, Helma K, Filip R |
Genes & development | 2023 |
How to Evaluate Fibrosis in IBD?
Tavares de Sousa H, Magro F |
2023 | |
Role of Interleukin-36 in inflammatory joint diseases.
Wang C, Hu J, Shi J |
Zhejiang da xue xue bao. Yi xue ban = Journal of Zhejiang University. Medical sciences | 2023 |
Interleukin-36γ is causative for liver damage upon infection with Rift Valley fever virus in type I interferon receptor-deficient mice
Anzaghe M, Niles MA, Korotkova E, Dominguez M, Kronhart S, Ortega Iannazzo S, Bechmann I, Bachmann M, Mühl H, Kochs G, Waibler Z |
Frontiers in immunology | 2023 |
Circulating inflammatory cytokines and psoriasis risk: A systematic review and meta-analysis
Liu XQ, Zhou PL, Yin XY, Wang AX, Wang DH, Yang Y, Liu Q |
PloS one | 2023 |
Elevated serum IL-36γ levels in patients with ankylosing spondylitis and its association with disease activity.
Shi S, Lu W, Zhou Y, Pang J, Li Y, Li M |
Molecular and Cellular Biochemistry | 2023 |
Prospective therapeutics for intestinal and hepatic fibrosis
Li X, Yu M, Zhao Q, Yu Y |
Bioengineering & Translational Medicine | 2023 |
The role of the interleukin-36 axis in generalized pustular psoriasis: a review of the mechanism of action of spesolimab
Hawkes JE, Visvanathan S, Krueger JG |
Frontiers in immunology | 2023 |
A Narrative Review of Cytokine Networks: Pathophysiological and Therapeutic Implications for Inflammatory Bowel Disease Pathogenesis
Vebr M, Pomahačová R, Sýkora J, Schwarz J |
Biomedicines | 2023 |
Increased Levels of Interleukin-36 in Obesity and Type 2 Diabetes Fuel Adipose Tissue Inflammation by Inducing Its Own Expression and Release by Adipocytes and Macrophages
G Frühbeck, J Gómez-Ambrosi, B Ramírez, A Mentxaka, A Rodríguez, S Becerril, G Reina, V Valentí, R Moncada, C Silva, V Catalán |
Frontiers in immunology | 2022 |
Therapeutic Targeting of Intestinal Fibrosis in Crohn’s Disease
G Santacroce, M Lenti, A Sabatino |
Cells | 2022 |
New and Emerging Targeted Therapies for Hidradenitis Suppurativa
A Čagalj, B Marinović, Z Mokos |
International journal of molecular sciences | 2022 |
IL‐36 γ and IL‐36Ra Reciprocally Regulate Colon Inflammation and Tumorigenesis by Modulating the Cell–Matrix Adhesion Network and Wnt Signaling
W Yang, H Dong, P Wang, Z Xu, J Xian, J Chen, H Wu, Y Lou, D Lin, B Zhong |
Advanced Science | 2022 |
Glucose Homeostasis in Relation to Neutrophil Mobilization in Smokers with COPD
Pournaras N, Andersson A, Kovach MA, Padra M, Che KF, Brundin B, Yoshihara S, Bozinovski S, Lindén SK, Jansson PA, Sköld MC, Qvarfordt I, Lindén A |
International journal of chronic obstructive pulmonary disease | 2022 |
Intestinal strictures in Crohn’s disease: a 2021 update
Lin X, Wang Y, Liu Z, Lin S, Tan J, He J, Hu F, Wu X, Ghosh S, Chen M, Liu F, Mao R |
Therapeutic advances in gastroenterology | 2022 |
Regulation of Interleukin-36γ/IL-36R Signaling Axis by PIN1 in Epithelial Cell Transformation and Breast Tumorigenesis
Poudel M, Bhattarai PY, Shrestha P, Choi HS |
Cancers | 2022 |
Plasma Levels of Interleukins 36α, 36β, and 37 in Patients with Psoriasis and Their Correlation with Disease Activity Parameters
Słucznowska-Głabowska S, Jaworska W, Staniszewska M, Tkacz M, Safranow K, Łuczkowska K, Zagrodnik E, Stecewicz I, Machaliński B, Pawlik A |
Journal of Clinical Medicine | 2022 |
CD147 Targeting by AC-73 Induces Autophagy and Reduces Intestinal Fibrosis Associated with TNBS Chronic Colitis.
Butera A, Quaranta MT, Crippa L, Spinello I, Saulle E, Di Carlo N, Campanile D, Boirivant M, Labbaye C |
Journal of Crohn's & colitis | 2022 |
Spesolimab: First Approval.
Blair HA |
Drugs | 2022 |
Increased ten-eleven translocation methylcytosine dioxygenase one in dorsal root ganglion contributes to inflammatory pain in CFA rats.
Liu Y, Zhang L, Xu ZH, Zhu J, Ma JL, Gao YP, Xu GY |
Molecular Pain | 2022 |
IL-1RAP, a Key Therapeutic Target in Cancer
Frenay J, Bellaye PS, Oudot A, Helbling A, Petitot C, Ferrand C, Collin B, Dias AM |
International journal of molecular sciences | 2022 |
The Cytokine Network in Colorectal Cancer: Implications for New Treatment Strategies
Braumüller H, Mauerer B, Andris J, Berlin C, Wieder T, Kesselring R |
Cells | 2022 |
Plasma IL-36α and IL-36γ as Potential Biomarkers in Interstitial Lung Disease Associated with Rheumatoid Arthritis: a Pilot Study in the Chinese Population.
Zheng W, Hu X, Zou M, Hu N, Song W, Wang R, Liu Y, Hou Q, Liu Y, Chen X, Cheng Z |
Inflammation | 2022 |
The role of interleukin-33 in organ fibrosis.
Di Carmine S, Scott MM, McLean MH, McSorley HJ |
2022 | |
Novel mechanisms and clinical trial endpoints in intestinal fibrosis*
J Wang, S Lin, JM Brown, D van Wagoner, C Fiocchi, F Rieder |
Immunological Reviews | 2021 |
Clinical Implementation of Biologics and Small Molecules in the Treatment of Hidradenitis Suppurativa
P Aarts, K Dudink, AR Vossen, KR van Straalen, CB Ardon, EP Prens, HH van der Zee |
Drugs | 2021 |
The Role of IL-36 in the Pathophysiological Processes of Autoimmune Diseases
W Chen, X Yu, XR Yuan, B Chen, N Cai, S Zeng, Y Sun, H Li |
Frontiers in pharmacology | 2021 |
Immunobiological Properties and Clinical Applications of Interleukin-38 for Immune-Mediated Disorders: A Systematic Review Study
A Esmaeilzadeh, N Bahmaie, E Nouri, MJ Hajkazemi, MZ Rafie |
International journal of molecular sciences | 2021 |
Development of Anti-fibrotic Therapy in Stricturing Crohn's Disease: Lessons from Randomized Trials in Other Fibrotic Diseases
S Lin, R Mao, C Qian, D Bettenworth, J Wang, J Li, D Bruining, V Jairath, B Feagan, M Chen, F Rieder |
Physiological reviews | 2021 |