Abstract
Background: The IL-17 (interleukin 17) family consists of six structurally related pro-inflammatory cytokines, namely IL-17A to IL-17F. These cytokines have garnered significant scientific interest due to their pivotal role in the pathogenesis of various diseases. Notably, a specific subset of T-cells expresses IL-17 family members, highlighting their importance in immune responses against microbial infections.
Introduction: IL-17 cytokines play a critical role in host defense mechanisms by inducing cytokines and chemokines, recruiting neutrophils, modifying T-cell differentiation, and stimulating the production of antimicrobial proteins. Maintaining an appropriate balance of IL-17 is vital for overall health. However, dysregulated production of IL-17A and other members can lead to the pathogenesis of numerous inflammatory and autoimmune diseases.
Method: This review provides a comprehensive overview of the IL-17 family and its involvement in several inflammatory and autoimmune diseases. Relevant literature and research studies were analyzed to compile the data presented in this review.
Results: IL-17 cytokines, particularly IL-17A, have been implicated in the development of various inflammatory and autoimmune disorders, including multiple sclerosis, Hashimoto's thyroiditis, systemic lupus erythematosus, pyoderma gangrenosum, autoimmune hepatic disorders, rheumatoid arthritis, psoriasis, psoriatic arthritis, ankylosing spondylitis, osteoarthritis, and graft-versus-host disease. Understanding the role of IL-17 in these diseases is crucial for developing targeted therapeutic strategies.
Conclusion: The significant involvement of IL-17 cytokines in inflammatory and autoimmune diseases underscores their potential as therapeutic targets. Current treatments utilizing antibodies against IL-17 cytokines and IL-17RA receptors have shown promise in managing these conditions. This review consolidates the understanding of IL-17 family members and their roles, providing valuable insights for the development of novel immunomodulators to effectively treat inflammatory and autoimmune diseases.
Keywords: Th17, IL-17, autoimmune disease, T cell, CD4+, cytokines.
[http://dx.doi.org/10.1128/IAI.01329-06] [PMID: 17403873]
[http://dx.doi.org/10.1086/422329] [PMID: 15243941]
[http://dx.doi.org/10.1111/j.1365-2249.2005.02842.x] [PMID: 16232206]
[http://dx.doi.org/10.1681/ASN.2010050536] [PMID: 21289213]
[http://dx.doi.org/10.1016/j.cyto.2015.07.029] [PMID: 26440138]
[http://dx.doi.org/10.1038/ni1497] [PMID: 17676044]
[http://dx.doi.org/10.1038/nri2295] [PMID: 18408735]
[http://dx.doi.org/10.1146/annurev.immunol.021908.132710] [PMID: 19132915]
[http://dx.doi.org/10.1016/j.cell.2010.02.021] [PMID: 20303875]
[http://dx.doi.org/10.1016/j.autrev.2013.12.004] [PMID: 24418308]
[http://dx.doi.org/10.1056/NEJMra0707449] [PMID: 19710487]
[http://dx.doi.org/10.1002/eji.201242605] [PMID: 22949323]
[http://dx.doi.org/10.1038/nrd3794] [PMID: 23023676]
[http://dx.doi.org/10.1111/j.1365-2567.2009.03240.x] [PMID: 20409152]
[http://dx.doi.org/10.1038/nri2800] [PMID: 20559326]
[http://dx.doi.org/10.1038/nri3707] [PMID: 25145755]
[http://dx.doi.org/10.1002/art.33507] [PMID: 22144400]
[http://dx.doi.org/10.1016/j.molmed.2016.01.001] [PMID: 26837266]
[http://dx.doi.org/10.1016/j.gene.2018.10.038] [PMID: 30342169]
[http://dx.doi.org/10.1164/rccm.200711-1648OC] [PMID: 18511701]
[http://dx.doi.org/10.3389/fimmu.2018.01682] [PMID: 30127781]
[http://dx.doi.org/10.1016/S1359-6101(03)00002-9] [PMID: 12651226]
[http://dx.doi.org/10.1016/j.immuni.2011.02.012] [PMID: 21349428]
[http://dx.doi.org/10.1016/j.fsi.2015.09.020] [PMID: 26364740]
[http://dx.doi.org/10.1016/j.fsi.2017.08.010] [PMID: 28811226]
[http://dx.doi.org/10.3390/ijms21072439] [PMID: 32244562]
[http://dx.doi.org/10.1016/j.dci.2020.103731] [PMID: 32387558]
[PMID: 22094986]
[http://dx.doi.org/10.1084/jem.20080321] [PMID: 18591412]
[http://dx.doi.org/10.1126/science.1200439] [PMID: 21350122]
[http://dx.doi.org/10.1016/j.cyto.2013.03.014] [PMID: 23557798]
[http://dx.doi.org/10.4049/jimmunol.179.8.5462] [PMID: 17911633]
[http://dx.doi.org/10.2147/JIR.S278335] [PMID: 33116747]
[http://dx.doi.org/10.1016/j.cellsig.2013.07.021] [PMID: 23917206]
[http://dx.doi.org/10.1016/j.cellsig.2010.11.022] [PMID: 21130872]
[http://dx.doi.org/10.1038/ncomms2880] [PMID: 23695682]
[http://dx.doi.org/10.1111/imm.12142] [PMID: 23819583]
[http://dx.doi.org/10.4049/jimmunol.1001153] [PMID: 20921529]
[http://dx.doi.org/10.1016/j.molimm.2017.07.004] [PMID: 28704706]
[http://dx.doi.org/10.4049/jimmunol.179.10.7128] [PMID: 17982105]
[http://dx.doi.org/10.1016/j.immuni.2015.03.008] [PMID: 25888259]
[http://dx.doi.org/10.18632/oncotarget.14835] [PMID: 28145881]
[http://dx.doi.org/10.1016/j.canlet.2018.02.037] [PMID: 29496538]
[http://dx.doi.org/10.18632/oncotarget.23008] [PMID: 29371916]
[http://dx.doi.org/10.1084/jem.20141702] [PMID: 25732306]
[http://dx.doi.org/10.1084/jem.20160581] [PMID: 28663436]
[http://dx.doi.org/10.1016/j.immuni.2011.09.010] [PMID: 21982598]
[http://dx.doi.org/10.1038/ni.2155] [PMID: 21993849]
[http://dx.doi.org/10.1038/ni.2156] [PMID: 21993848]
[http://dx.doi.org/10.1038/ncomms2127] [PMID: 23047677]
[http://dx.doi.org/10.1016/j.clim.2013.10.001] [PMID: 24211715]
[http://dx.doi.org/10.1038/ncomms7669] [PMID: 25808990]
[http://dx.doi.org/10.1074/jbc.M114.586560] [PMID: 25378394]
[http://dx.doi.org/10.1016/j.celrep.2016.07.075] [PMID: 27545889]
[http://dx.doi.org/10.1016/j.cytogfr.2010.10.002] [PMID: 21074482]
[http://dx.doi.org/10.1111/j.0300-9475.2004.01443.x] [PMID: 15320879]
[http://dx.doi.org/10.4049/jimmunol.169.1.443] [PMID: 12077275]
[http://dx.doi.org/10.1084/jem.20061738] [PMID: 17200411]
[http://dx.doi.org/10.1038/nature08636] [PMID: 20023630]
[http://dx.doi.org/10.1126/scitranslmed.3009124] [PMID: 25273095]
[http://dx.doi.org/10.1016/j.jaci.2018.03.019] [PMID: 29778504]
[http://dx.doi.org/10.1074/jbc.C600322200] [PMID: 17218320]
[http://dx.doi.org/10.4049/jimmunol.179.6.4135] [PMID: 17785852]
[http://dx.doi.org/10.1016/B978-0-12-812630-1.00014-1]
[http://dx.doi.org/10.1177/0300060513501751] [PMID: 24319050]
[PMID: 20430731]
[http://dx.doi.org/10.1186/s13075-015-0847-3] [PMID: 26653257]
[http://dx.doi.org/10.1016/j.joca.2005.10.004] [PMID: 16311048]
[http://dx.doi.org/10.1053/joca.2002.0829] [PMID: 12359166]
[http://dx.doi.org/10.1111/j.1365-2133.2008.08902.x] [PMID: 19016708]
[http://dx.doi.org/10.4103/0019-5154.62752] [PMID: 20606886]
[http://dx.doi.org/10.1007/s11010-011-1036-6] [PMID: 21894442]
[http://dx.doi.org/10.1002/art.38376] [PMID: 24470327]
[http://dx.doi.org/10.1002/art.21749] [PMID: 16572447]
[http://dx.doi.org/10.2353/ajpath.2008.070690] [PMID: 18156204]
[http://dx.doi.org/10.1096/fj.09-141978] [PMID: 19940258]
[PMID: 23146786]
[http://dx.doi.org/10.1080/08916934.2016.1183654] [PMID: 27206624]
[http://dx.doi.org/10.1177/2042018820907013] [PMID: 32128107]
[http://dx.doi.org/10.1093/toxsci/kfy019] [PMID: 29385629]
[http://dx.doi.org/10.4103/ijem.IJEM_412_16] [PMID: 28670539]
[http://dx.doi.org/10.1002/eji.201141751] [PMID: 22002883]
[http://dx.doi.org/10.4049/jimmunol.0902822] [PMID: 20363968]
[http://dx.doi.org/10.4049/jimmunol.1001860] [PMID: 20810982]
[http://dx.doi.org/10.1016/j.jhep.2018.12.035] [PMID: 30641095]
[http://dx.doi.org/10.1007/s11914-009-0004-5] [PMID: 19239825]
[http://dx.doi.org/10.1101/2020.09.27.20202762]
[http://dx.doi.org/10.1111/bjd.16050] [PMID: 28991370]
[http://dx.doi.org/10.1016/j.clim.2008.01.019] [PMID: 18373953]
[http://dx.doi.org/10.1016/j.ejim.2010.03.004] [PMID: 20493423]
[http://dx.doi.org/10.1007/s40744-021-00380-2] [PMID: 34618347]
[http://dx.doi.org/10.3899/jrheum.201111] [PMID: 33722947]
[http://dx.doi.org/10.1007/s40744-020-00269-6] [PMID: 33351179]
[http://dx.doi.org/10.1136/rmdopen-2018-000749] [PMID: 30564451]
[http://dx.doi.org/10.1002/acr2.11139] [PMID: 32352653]
[http://dx.doi.org/10.1111/1756-185X.13094] [PMID: 28544533]
[http://dx.doi.org/10.1080/00207454.2016.1231186] [PMID: 27595159]
[http://dx.doi.org/10.1155/2012/260473] [PMID: 23091305]
[http://dx.doi.org/10.1080/1744666X.2018.1438269] [PMID: 29406827]
[http://dx.doi.org/10.1111/iwj.13389] [PMID: 32378319]
[http://dx.doi.org/10.1111/bjd.15226] [PMID: 27943240]
[http://dx.doi.org/10.1016/j.jdcr.2020.08.033] [PMID: 32953958]
[http://dx.doi.org/10.1016/j.jaad.2020.05.007] [PMID: 32416208]
[http://dx.doi.org/10.1371/journal.pone.0018909] [PMID: 21526159]
[http://dx.doi.org/10.1038/icb.2011.59] [PMID: 21691280]
[http://dx.doi.org/10.1002/jbmr.2228] [PMID: 24677326]
[http://dx.doi.org/10.3899/jrheum.150182] [PMID: 26773108]
[http://dx.doi.org/10.1016/S0140-6736(21)00440-2] [PMID: 33894834]
[http://dx.doi.org/10.1111/jdv.17071] [PMID: 33617042]
[http://dx.doi.org/10.1002/eji.200636658] [PMID: 17048275]
[http://dx.doi.org/10.1002/eji.200636484] [PMID: 17039570]
[http://dx.doi.org/10.1182/blood-2012-02-412726] [PMID: 22976954]
[http://dx.doi.org/10.1111/jdv.12996] [PMID: 25693783]
[http://dx.doi.org/10.1111/jdv.14237] [PMID: 28322474]
[http://dx.doi.org/10.1002/art.38617] [PMID: 24623718]
[http://dx.doi.org/10.3899/jrheum.140831] [PMID: 26669919]
[http://dx.doi.org/10.1126/scitranslmed.3001107] [PMID: 20926833]
[http://dx.doi.org/10.1093/rheumatology/kev258] [PMID: 26268815]
[http://dx.doi.org/10.1183/1393003.congress-2017.OA2897]
[http://dx.doi.org/10.1016/j.ophtha.2014.12.033] [PMID: 25638011]
[PMID: 31025924]
[http://dx.doi.org/10.1007/s13555-021-00554-4] [PMID: 34060012]
[http://dx.doi.org/10.3899/jrheum.141271] [PMID: 25877498]
[http://dx.doi.org/10.1164/rccm.201212-2318OC] [PMID: 24200404]
[http://dx.doi.org/10.1056/NEJMoa1315231] [PMID: 24918373]