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Mechanisms

Interleukin (IL)-33 immunobiology in asthma and airway inflammatory diseases

, MSc, PhDORCID Icon & , MD
Pages 2530-2538 | Received 02 Sep 2021, Accepted 15 Dec 2021, Published online: 27 Dec 2021

References

  • Cayrol C, Girard JP. Interleukin-33 (IL-33): A nuclear cytokine from the IL-1 family. Immunol Rev 2018;281(1):154–168. doi:10.1111/imr.12619.
  • Gatti F, Mia S, Hammarstrom C, Frerker N, Fosby B, Wang J, Pietka W, Sundnes O, Hol J, Kasprzycka M, et al. Nuclear IL-33 restrains the early conversion of fibroblasts to an extracellular matrix-secreting phenotype. Sci Rep 2021;11(1):108. doi:10.1038/s41598-020-80509-5.
  • Gaurav R, Varasteh JT, Weaver MR, Jacobson SR, Hernandez-Lagunas L, Liu Q, Nozik-Grayck E, Chu HW, Alam R, Nordestgaard BG, et al. The R213G polymorphism in SOD3 protects against allergic airway inflammation. JCI Insight 2017;2(17):e95072. doi:10.1172/jci.insight.95072.
  • Drake LY, Bartemes KR, Bachman KA, Hagan JB, Kita H. In vitro culture with cytokines provides a tool to assess the effector functions of ILC2s in peripheral blood in asthma. J Asthma Allergy 2021; 14:13–22. doi:10.2147/JAA.S286695.
  • Johnson AN, Harkema JR, Nelson AJ, Dickinson JD, Kalil J, Duryee MJ, Thiele GM, Kumar B, Singh AB, Gaurav R, et al. MyD88 regulates a prolonged adaptation response to environmental dust exposure-induced lung disease. Respir Res 2020;21(1):97. doi:10.1186/s12931-020-01362-8.
  • Dinarello CA. The IL-1 family of cytokines and receptors in rheumatic diseases. Nat Rev Rheumatol 2019;15(10):612–632. doi:10.1038/s41584-019-0277-8.
  • Travers J, Rochman M, Miracle CE, Habel JE, Brusilovsky M, Caldwell JM, Rymer JK, Rothenberg ME. Chromatin regulates IL-33 release and extracellular cytokine activity. Nat Commun 2018;9(1):3244. doi:10.1038/s41467-018-05485-x.
  • Wu K, Kamimoto K, Zhang Y, Yang K, Keeler SP, Gerovac BJ, Agapov EV, Austin SP, Yantis J, Gissy KA, et al. Basal-epithelial stem cells cross an alarmin checkpoint for post-viral lung disease. J Clin Invest 2021;131(19):e149336. doi:10.1172/JCI149336.
  • Liu X, Hammel M, He Y, Tainer JA, Jeng US, Zhang L, Wang S, Wang X. Structural insights into the interaction of IL-33 with its receptors. Proc Natl Acad Sci USA 2013;110(37):14918–14923. doi:10.1073/pnas.1308651110.
  • Pivniouk V, Gimenes-Junior JA, Ezeh P, Michael A, Pivniouk O, Hahn S, VanLinden SR, Malone SP, Abidov A, Anderson D, et al. Airway administration of OM-85, a bacterial lysate, blocks experimental asthma by targeting dendritic cells and the epithelium/IL-33/ILC2 axis. J Allergy Clin Immunol 2021. doi:10.1016/j.jaci.2021.09.013.
  • Gordon ED, Palandra J, Wesolowska-Andersen A, Ringel L, Rios CL, Lachowicz-Scroggins ME, Sharp LZ, Everman JL, MacLeod HJ, Lee JW, Mason RJ, Matthay MA, et al. IL1RL1 asthma risk variants regulate airway type 2 inflammation. JCI Insight 2016;1(14):e87871. doi:10.1172/jci.insight.87871.
  • Queiroz GA, Costa RS, Alcantara-Neves NM, Nunes de Oliveira Costa G, Barreto ML, Carneiro VL, Figueiredo CA. IL33 and IL1RL1 variants are associated with asthma and atopy in a Brazilian population. Int J Immunogenet 2017;44(2):51–61. doi:10.1111/iji.12306.
  • Aneas I, Decker DC, Howard CL, Sobreira DR, Sakabe NJ, Blaine KM, Stein MM, Hrusch CL, Montefiori LE, Tena J, Magnaye KM, Clay SM, et al. Asthma-associated genetic variants induce IL33 differential expression through an enhancer-blocking regulatory region. Nat Commun 2021;12(1):6115. doi:10.1038/s41467-021-26347-z.
  • Riikonen R, Terasjarvi J, Lauhkonen E, Nuolivirta K, He Q, Korppi M. Interleukine-1 receptor like-1 rs13408661/13431828 polymorphism is associated with persistent post-bronchiolitis asthma at school age. Acta Paediatr 2021. doi:10.1111/apa.16176.
  • Latiano A, Palmieri O, Pastorelli L, Vecchi M, Pizarro TT, Bossa F, Merla G, Augello B, Latiano T, Corritore G, et al. Associations between genetic polymorphisms in IL-33, IL1R1 and risk for inflammatory bowel disease. PLoS One 2013;8(4):e62144. doi:10.1371/journal.pone.0062144.
  • Rustowska‐Rogowska A, Gleń J, Jarząbek T, Rogowski W, Rębała K, Zabłotna M, Czajkowska K, Nowicki R, Kowalczyk A, Sokołowska‐Wojdyło M. Interleukin-33 polymorphisms and serum concentrations in mycosis fungoides. Int J Dermatol 2020;59(3):345–351. doi:10.1111/ijd.14696.
  • Fan D, Ding N, Yang T, Wu S, Liu S, Liu L, Hu Y, Duan Z, Xia G, Xu S, et al. Single nucleotide polymorphisms of the interleukin-33 (IL-33) gene are associated with ankylosing spondylitis in Chinese individuals: a case-control pilot study. Scand J Rheumatol 2014;43(5):374–379. doi:10.3109/03009742.2014.882408.
  • Angeles-Martinez J, Posadas-Sanchez R, Llorente L, Alvarez-Leon E, Ramirez-Bello J, Villarreal-Molina T, Lima G, Cardoso-Saldana G, Rodriguez-Perez JM, Perez-Hernandez N, et al. The rs7044343 polymorphism of the interleukin 33 gene is associated with decreased risk of developing premature coronary artery disease and central obesity, and could be involved in regulating the production of IL-33. PLoS One 2017;12(1):e0168828. doi:10.1371/journal.pone.0168828.
  • Falahi S, Karaji AG, Koohyanizadeh F, Rezaiemanesh A, Salari F. A comprehensive in Silico analysis of the functional and structural impact of single nucleotide polymorphisms (SNPs) in the human IL-33 gene. Comput Biol Chem 2021; 94:107560. doi:10.1016/j.compbiolchem.2021.107560.
  • Gordon ED, Simpson LJ, Rios CL, Ringel L, Lachowicz-Scroggins ME, Peters MC, Wesolowska-Andersen A, Gonzalez JR, MacLeod HJ, Christian LS, Yuan S, et al. Alternative splicing of interleukin-33 and type 2 inflammation in asthma. Proc Natl Acad Sci USA 2016;113(31):8765–8770. doi:10.1073/pnas.1601914113.
  • Hong J, Bae S, Jhun H, Lee S, Choi J, Kang T, Kwak A, Hong K, Kim E, Jo S, et al. Identification of constitutively active interleukin 33 (IL-33) splice variant. J Biol Chem 2011;286(22):20078–20086. doi:10.1074/jbc.M111.219089.
  • Scott IC, Majithiya JB, Sanden C, Thornton P, Sanders PN, Moore T, Guscott M, Corkill DJ, Erjefalt JS, Cohen ES. Interleukin-33 is activated by allergen- and necrosis-associated proteolytic activities to regulate its alarmin activity during epithelial damage. Sci Rep 2018;8(1):3363. doi:10.1038/s41598-018-21589-2.
  • Hayakawa H, Hayakawa M, Tominaga SI. Soluble ST2 suppresses the effect of interleukin-33 on lung type 2 innate lymphoid cells. Biochem Biophys Rep 2016; 5:401–407. doi:10.1016/j.bbrep.2016.02.002.
  • Hasan A, Kochumon S, Al-Ozairi E, Tuomilehto J, Al-Mulla F, Ahmad R. Correlation profile of suppression of tumorigenicity 2 and/or interleukin-33 with biomarkers in the adipose tissue of individuals with different metabolic states. Diabetes Metab Syndr Obes 2020; 13:3839–3859. doi:10.2147/DMSO.S251978.
  • Palmer G, Lipsky BP, Smithgall MD, Meininger D, Siu S, Talabot-Ayer D, Gabay C, Smith DE. The IL-1 receptor accessory protein (AcP) is required for IL-33 signaling and soluble AcP enhances the ability of soluble ST2 to inhibit IL-33. Cytokine 2008;42(3):358–364. doi:10.1016/j.cyto.2008.03.008.
  • Watanabe M, Nakamoto K, Inui T, Sada M, Honda K, Tamura M, Ogawa Y, Yokoyama T, Saraya T, Kurai D, et al. Serum sST2 levels predict severe exacerbation of asthma. Respir Res 2018;19(1):169. doi:10.1186/s12931-018-0872-2.
  • Tajima S, Oshikawa K, Tominaga S, Sugiyama Y. The increase in serum soluble ST2 protein upon acute exacerbation of idiopathic pulmonary fibrosis. Chest 2003;124(4):1206–1214. doi:10.1378/chest.124.4.1206.
  • Tworek D, Majewski S, Szewczyk K, Kiszalkiewicz J, Kurmanowska Z, Gorski P, Brzezianska-Lasota E, Kuna P, Antczak A. The association between airway eosinophilic inflammation and IL-33 in stable non-atopic COPD. Respir Res 2018; 19:108. doi:10.1186/s12931-018-0807-y.
  • Ragusa R, Basta G, Del Turco S, Caselli C. A possible role for ST2 as prognostic biomarker for COVID-19. Vascul Pharmacol 2021; 138:106857. doi:10.1016/j.vph.2021.106857.
  • Bertheloot D, Latz E. HMGB1, IL-1α, IL-33 and S100 proteins: dual-function alarmins. Cell Mol Immunol 2017;14(1):43–64. doi:10.1038/cmi.2016.34.
  • Roussel L, Erard M, Cayrol C, Girard JP. Molecular mimicry between IL-33 and KSHV for attachment to chromatin through the H2A-H2B acidic pocket. EMBO Rep 2008;9(10):1006–1012. doi:10.1038/embor.2008.145.
  • Choi YS, Park JA, Kim J, Rho SS, Park H, Kim YM, Kwon YG. Nuclear IL-33 is a transcriptional regulator of NF-κB p65 and induces endothelial cell activation. Biochem Biophys Res Commun 2012;421(2):305–311. doi:10.1016/j.bbrc.2012.04.005.
  • Ramazi S, Zahiri J. Posttranslational modifications in proteins: resources, tools and prediction methods. Database (Oxford) 2021; 2021:2021. doi:10.1093/database/baab012.
  • Fu Z, Thorpe M, Alemayehu R, Roy A, Kervinen J, de Garavilla L, Abrink M, Hellman L. Highly selective cleavage of cytokines and chemokines by the human mast cell chymase and neutrophil cathepsin G. J Immunol 2017;198(4):1474–1483. doi:10.4049/jimmunol.1601223.
  • Fu Z, Akula S, Thorpe M, Hellman L. Potent and broad but not unselective cleavage of cytokines and chemokines by human neutrophil elastase and proteinase 3. Int J Mol Sci 2020;21(2):651. doi:10.3390/ijms21020651.
  • Bae S, Kang T, Hong J, Lee S, Choi J, Jhun H, Kwak A, Hong K, Kim E, Jo S, et al. Contradictory functions (activation/termination) of neutrophil proteinase 3 enzyme (PR3) in interleukin-33 biological activity. J Biol Chem 2012;287(11):8205–8213. doi:10.1074/jbc.M111.295055.
  • Zhao J, Wei J, Mialki RK, Mallampalli DF, Chen BB, Coon T, Zou C, Mallampalli RK, Zhao Y. F-box protein FBXL19-mediated ubiquitination and degradation of the receptor for IL-33 limits pulmonary inflammation. Nat Immunol 2012;13(7):651–658. doi:10.1038/ni.2341.
  • Tao L, Chen C, Song H, Piccioni M, Shi G, Li B. Deubiquitination and stabilization of IL-33 by USP21. Int J Clin Exp Pathol 2014;7(8):4930–4937.
  • Ni Y, Tao L, Chen C, Song H, Li Z, Gao Y, Nie J, Piccioni M, Shi G, Li B. The deubiquitinase USP17 regulates the stability and nuclear function of IL-33. Int J Mol Sci 2015;16(11):27956–27966. doi:10.3390/ijms161126063.
  • Cohen ES, Scott IC, Majithiya JB, Rapley L, Kemp BP, England E, Rees DG, Overed-Sayer CL, Woods J, Bond NJ, et al. Oxidation of the alarmin IL-33 regulates ST2-dependent inflammation. Nat Commun 2015; 6:8327. doi:10.1038/ncomms9327.
  • Matsui R, Ferran B, Oh A, Croteau D, Shao D, Han J, Pimentel DR, Bachschmid MM. Redox regulation via glutaredoxin-1 and protein S-glutathionylation. Antioxid Redox Signal 2020;32(10):677–700. doi:10.1089/ars.2019.7963.
  • Weinberg EO, Ferran B, Tsukahara Y, Hatch MMS, Han J, Murdoch CE, Matsui R. IL-33 induction and signaling are controlled by glutaredoxin-1 in mouse macrophages. PLoS One 2019;14(1):e0210827. doi:10.1371/journal.pone.0210827.
  • Srisomboon Y, Ohkura N, Iijima K, Kobayashi T, Maniak PJ, Kita H, O’Grady SM. Airway exposure to polyethyleneimine nanoparticles induces type 2 immunity by a mechanism involving oxidative stress and ATP release. Int J Mol Sci 2021;22(16):9071. doi:10.3390/ijms22169071.
  • Gaurav R, Bewtra AK, Agrawal DK. Chloride channel 3 channels in the activation and migration of human blood eosinophils in allergic asthma. Am J Respir Cell Mol Biol 2015;53(2):235–245. doi:10.1165/rcmb.2014-0300OC.
  • Warren KJ, Poole JA, Sweeter JM, DeVasure JM, Dickinson JD, Peebles RS, Jr., Wyatt TA. Neutralization of IL-33 modifies the type 2 and type 3 inflammatory signature of viral induced asthma exacerbation. Respir Res 2021;22(1):206. doi:10.1186/s12931-021-01799-5.
  • van de Veen W, Akdis M. The use of biologics for immune modulation in allergic disease. J Clin Invest 2019;129(4):1452–1462. doi:10.1172/JCI124607.
  • Nnane I, Frederick B, Yao Z, Raible D, Shu C, Badorrek P, van den Boer M, Branigan P, Duffy K, Baribaud F, et al. The first-in-human study of CNTO 7160, an anti-interleukin-33 receptor monoclonal antibody, in healthy subjects and patients with asthma or atopic dermatitis. Br J Clin Pharmacol 2020;86(12):2507–2518. doi:10.1111/bcp.14361.
  • Okragly AJ, Corwin KB, Elia M, He D, Schroeder O, Zhang Q, Shiyanova T, Bright S, Dicker SB, Chlewicki L, et al. Generation and characterization of torudokimab (LY3375880): A monoclonal antibody that neutralizes interleukin-33. J Inflamm Res 2021; 14:3823–3835. doi:10.2147/JIR.S320287.
  • Holgado A, Braun H, Van Nuffel E, Detry S, Schuijs MJ, Deswarte K, Vergote K, Haegman M, Baudelet G, Haustraete J, et al. IL-33trap is a novel IL-33-neutralizing biologic that inhibits allergic airway inflammation. J Allergy Clin Immunol 2019;144(1):204–215. doi:10.1016/j.jaci.2019.02.028.
  • Holgado A, Braun H, Verstraete K, Vanneste D, Callewaert N, Savvides SN, Afonina IS, Beyaert R. Single-chain soluble receptor fusion proteins as versatile cytokine inhibitors. Front Immunol 2020; 11:1422.
  • Xu W, Li R, Sun Y. Increased IFN-gamma-producing Th17/Th1 cells and their association with lung function and current smoking status in patients with chronic obstructive pulmonary disease. BMC Pulm Med 2019; 19:137. doi:10.1186/s12890-019-0899-2.
  • Gaurav R, Anderson DR, Radio SJ, Bailey KL, England BR, Mikuls TR, Thiele GM, Strah HM, Romberger DJ, Wyatt TA, et al. IL-33 Depletion in COVID-19 lungs. Chest 2021;160(5):1656–1659. doi:10.1016/j.chest.2021.06.058.
  • de Llano LP, Cosio BG, Iglesias A, de Las Cuevas N, Soler-Cataluna JJ, Izquierdo JL, Lopez-Campos JL, Calero C, Plaza V, Miravitlles M, et al. Mixed Th2 and non-Th2 inflammatory pattern in the asthma-COPD overlap: a network approach. COPD 2018;13:591–601. doi:10.2147/COPD.S153694.
  • Joo H, Park SJ, Min KH, Rhee CK. Association between plasma interleukin-33 level and acute exacerbation of chronic obstructive pulmonary disease. BMC Pulm Med 2021; 21:86. doi:10.1186/s12890-021-01423-8.
  • Jiang M, Cai R, Wang J, Li Z, Xu D, Jing J, Zhang F, Li F, Ding J. ILC2 cells promote Th2 cell differentiation in AECOPD through activated notch-GATA3 signaling pathway. Front Immunol 2021; 12(685400):685400.
  • Kim SW, Rhee CK, Kim KU, Lee SH, Hwang HG, Kim YI, Kim DK, Lee SD, Oh YM, Yoon HK. Factors associated with plasma IL-33 levels in patients with chronic obstructive pulmonary disease. Int J Chron Obstruct Pulmon Dis 2017; 12:395–402. doi:10.2147/COPD.S120445.
  • Gorska K, Nejman-Gryz P, Paplinska-Goryca M, Korczynski P, Prochorec-Sobieszek M, Krenke R. Comparative study of IL-33 and IL-6 levels in different respiratory samples in mild-to-moderate asthma and COPD. COPD 2018;15(1):36–45. doi:10.1080/15412555.2017.1416074.
  • Byers DE, Alexander-Brett J, Patel AC, Agapov E, Dang-Vu G, Jin X, Wu K, You Y, Alevy Y, Girard JP, et al. Long-term IL-33-producing epithelial progenitor cells in chronic obstructive lung disease. J Clin Invest 2013;123(9):3967–3982. doi:10.1172/JCI65570.
  • Doni A, Mantovani A, Bottazzi B, Russo RC. PTX3 regulation of inflammation, hemostatic response, tissue repair, and resolution of fibrosis favors a role in limiting idiopathic pulmonary fibrosis. Front Immunol 2021; 12:676702.
  • Lee JU, Chang HS, Lee HJ, Jung CA, Bae DJ, Song HJ, Park JS, Uh ST, Kim YH, Seo KH, Park CS. Upregulation of interleukin-33 and thymic stromal lymphopoietin levels in the lungs of idiopathic pulmonary fibrosis. BMC Pulm Med 2017;17(1):39. doi:10.1186/s12890-017-0380-z.
  • Majewski S, Szewczyk K, Bialas AJ, Milkowska-Dymanowska J, Gorski P, Piotrowski WJ. Epithelial alarmins in serum and exhaled breath in patients with idiopathic pulmonary fibrosis: a prospective one-year follow-up cohort study. J Clin Med 2019; 8(10):1590. doi:10.3390/jcm8101590.
  • Shieh JM, Tseng HY, Jung F, Yang SH, Lin JC. Elevation of IL-6 and IL-33 levels in serum associated with lung fibrosis and skeletal muscle wasting in a bleomycin-induced lung injury mouse model. Mediators Inflamm 2019; 2019:1–12. doi:10.1155/2019/7947596.
  • Xiong Y, Cui X, Zhou Y, Chai G, Jiang X, Ge G, Wang Y, Sun H, Che H, Nie Y, et al. Dehydrocostus lactone inhibits BLM-induced pulmonary fibrosis and inflammation in mice via the JNK and p38 MAPK-mediated NF-κB signaling pathways . Int Immunopharmacol 2021; 98:107780. doi:10.1016/j.intimp.2021.107780.
  • Xiangyang Z, Lutian Y, Lin Z, Liping X, Hui S, Jing L. Increased levels of interleukin-33 associated with bone erosion and interstitial lung diseases in patients with rheumatoid arthritis. Cytokine 2012;58(1):6–9. doi:10.1016/j.cyto.2011.12.010.
  • Mikuls TR, Gaurav R, Thiele GM, England BR, Wolfe MG, Shaw BP, Bailey KL, Wyatt TA, Nelson AJ, Duryee MJ, et al. The impact of airborne endotoxin exposure on rheumatoid arthritis-related joint damage, autoantigen expression, autoimmunity, and lung disease. Int Immunopharmacol 2021; 100:108069. doi:10.1016/j.intimp.2021.108069.
  • Burke H, Freeman A, Cellura DC, Stuart BL, Brendish NJ, Poole S, Borca F, Phan HTT, Sheard N, Williams S, et al., REACT COVID investigators. Inflammatory phenotyping predicts clinical outcome in COVID-19. Respir Res 2020;21(1):245. doi:10.1186/s12931-020-01511-z.
  • Menzel M, Akbarshahi H, Mahmutovic Persson I, Andersson C, Puthia M, Uller L. NFkappaB1 dichotomously regulates pro-inflammatory and antiviral responses in asthma. J Innate Immun 2021; 1–10. doi:10.1159/000517847.
  • Georgakis S, Gkirtzimanaki K, Papadaki G, Gakiopoulou H, Drakos E, Eloranta ML, Makridakis M, Kontostathi G, Zoidakis J, Baira E, et al. NETs decorated with bioactive IL-33 infiltrate inflamed tissues and induce IFN-alpha production in patients with SLE. JCI Insight 2021;6(21):e147671. doi:10.1172/jci.insight.147671.
  • Molofsky AB, Van Gool F, Liang HE, Van Dyken SJ, Nussbaum JC, Lee J, Bluestone JA, Locksley RM. Interleukin-33 and interferon-γ counter-regulate group 2 innate lymphoid cell activation during immune perturbation. Immunity 2015;43(1):161–174. doi:10.1016/j.immuni.2015.05.019.
  • Bao Q, Lv R, Lei M. IL-33 attenuates mortality by promoting IFN-γ production in sepsis . Inflamm Res 2018;67(6):531–538. doi:10.1007/s00011-018-1144-9.
  • Kopach P, Lockatell V, Pickering EM, Haskell RE, Anderson RD, Hasday JD, Todd NW, Luzina IG, Atamas SP. IFN-γ directly controls IL-33 protein level through a STAT1- and LMP2-dependent mechanism . J Biol Chem 2014;289(17):11829–11843. doi:10.1074/jbc.M113.534396.
  • Rouchka EC, Chariker JH, Alejandro B, Adcock RS, Singhal R, Ramirez J, Palmer KE, Lasnik AB, Carrico R, Arnold FW, et al. Induction of interferon response by high viral loads at early stage infection may protect against severe outcomes in COVID-19 patients. Sci Rep 2021;11(1):15715. doi:10.1038/s41598-021-95197-y.

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