mimmunМедицинская иммунологияMedical Immunology (Russia)1563-06252313-741XSPb RAACI10.15789/1563-0625-MOI-1949mimmun-1949Research ArticleОБЗОРЫREVIEWSМеханизмы врожденного иммунитета в патогенезе псориаза: подходы к таргетной терапииMechanisms of innate immunity in pathogenesis of psoriasis: approaches to targeted therapyhttps://orcid.org/0000-0003-0013-8651МеркушоваЕ. Д.MerkushovaE. D.

Меркушова Екатерина Дмитриевна – ассистент кафедры иммунологии медико-биологического факультета

117997, Москва, ул. Островитянова, 1Тел.: 8 (915) 256-96-94 

Merkushova Ekaterina D. – Assistant Professor, Department of Immunology

117997, Russian Federation, Moscow, Ostrovityanov str., 1Phone: 7 (915) 256-96-94 

Rina.karmin@outlook.comhttps://orcid.org/0000-0002-6735-4693ХасановаЕ. М.KhasanovaE. M.

старший лаборант кафедры иммунологии медико-биологического факультета

Москва

Senior Laboratory Assistant, Department of Immunology

Moscow

joimolino@gmail.comhttps://orcid.org/0000-0003-1271-3078ГанковскаяЛ. В.GankovskayaL. V.

д.м.н., профессор, заведующая кафедрой иммунологии медико-биологического факультета

Москва

PhD, MD (Medicine), Professor, Head, Department of Immunology

Moscow

lvgan@yandex.ruФГАОУ ВО «Российский национальный исследовательский медицинский университет имени Н.И. Пирогова» Министерства здравоохранения РФРоссияN. Pirogov Russian National Research Medical UniversityRussian Federation202020052020223449458Copyright © Меркушова Е.Д., Хасанова Е.М., Ганковская Л.В., 20202020Меркушова Е.Д., Хасанова Е.М., Ганковская Л.В.Merkushova E.D., Khasanova E.M., Gankovskaya L.V.Данная работа распространяется под лицензией Creative Commons Attribution 4.0.This work is licensed under a Creative Commons Attribution 4.0 License.https://www.mimmun.ru/mimmun/article/view/1949

Псориаз является хроническим аутовоспалительным, генетически детерминированным дерматозом мультифакториальной природы, для которого характерна гиперпролиферация эпидермиса, нарушение дифференцировки кератиноцитов, а также воспалительная реакция в дерме. Заболевание характеризуется тенденцией к распространению площади поражения и вовлечением в патологический процесс суставной ткани, что значительно сказывается на уровне жизни больных и ведет к их инвалидизации. Известно множество провоцирующих факторов, способствующих возникновению псориаза или прогрессированию уже существующего псориатического процесса у лиц с генетической предрасположенностью. К ним относят неблагоприятные климатические условия, травматизацию кожи, воздействие ультрафиолета, ожоги, инфекции и др.

В данном обзоре описана роль врожденного иммунитета в патогенезе псориаза, а также подробно рассмотрены механизмы участия PAMPs и DAMPs в индукции воспаления. При псориазе одним из наиболее веротяных DAMPs является положительно заряженный кателицидин, способный образовывать комплекс с отрицательно заряженными клеточными полианионами – LL-37/ауто-РНК и LL-37/ауто-ДНК. Взаимодействие лигандов PAMPs/DAMPs со своими рецепторами PRRs ведет к инициации сигнала, ответом на который является активация эффекторных компонентов иммунной системы: запуск сборки инфламмасомного комплекса, активация каспаз, синтез провоспалительных цитокинов и процессинг их незрелых форм.

В обзоре уделено внимание роли TLRs в условиях физиологической нормы, которые распознают сигналы опасности и обеспечивают защиту от патогенов и их своевременную элиминацию, и при развитии патологического процесса. Активация TLRs индуцирует выработку провоспалительных цитокинов, интерферонов и противомикробных пептидов, хемокинов, которые поддерживают развитие псориатического воспаления.

Помимо TLRs, подробно описаны механизмы участия инфламмасомного комплекса в развитии псориаза, который обеспечивает процессинг зрелых форм IL-1β и IL-18. Зрелые формы этих цитокинов опосредуют развитие воспаления в псориатическом очаге. Кроме того, процессинг этих цитокинов каспазами по механизму положительной обратной связи дает дополнительный сигнал к активации транскрипционной активности их генов и способствует хронизации воспаления.

В обзоре представлены данные, подтверждающие участие инфламмасомного воспаления в патогенезе псориаза. Большое внимание уделено описанию фармакологических ингибиторов инфламмасомы, которые в будущем могут быть препаратами выбора для терапии воспалительных заболеваний. Исследование молекулярных механизмов системы врожденного иммунитета позволит выявить новые подходы к прогнозу и разработке таргетной терапии псориаза.

Psoriasis is a chronic auto-inflammatory, genetically determined dermatosis, being multifactorial by origin, characterized by hyperproliferation of epidermis, affected keratinocyte differentiation and inflammatory reaction in dermis. The disease is characterized by a tendency to spread over the area of lesion, and involvement of articular tissue in the pathological process, which significantly affects the living standards of patients and causes their disability. There are many provoking factors that contribute to occurrence of psoriasis, or progression of existing psoriatic process in individuals with a genetic predisposition. These factors include adverse climatic conditions, skin trauma, exposure to ultraviolet light, burns, infections, etc.

This review describes the role of innate immunity in pathogenesis of psoriasis, and describes in detail the mechanisms involved into induction of inflammation of PAMPs and DAMPs. In psoriasis, positively charged catelicidin is considered one of the most important DAMPs, which can form a complex with negatively charged cell polyanions-LL-37/auto-RNA and LL-37/auto-DNA. The interaction of PAMP/DAMP ligands with specific PRR receptors leads to signal activation of effector components of immune system, i.e., assembly of inflammasome complex, caspase activation, synthesis of inflammatory cytokines and processing of their immature forms. The review focuses on the role of TLRs under the conditions of physiological norm, which recognize danger signals and provide protection from pathogens and their timely elimination, and in development of pathological process. Activation of TLRs induces the production of pro-inflammatory cytokines, interferons and antimicrobial peptides, chemokines that support the development of psoriatic inflammation.

In addition to TLRs, the mechanisms of involvement of inflammasomes in the development of psoriasis, which provides processing of mature forms of IL-1β and IL-18, are described in detail. Mature forms of these cytokines mediate the development of inflammation in psoriatic focus. In addition, processing of these cytokines by caspases using the positive feedback mechanism provides an additional signal to activate transcriptional activity of their genes and contributes to perpetuated inflammation.

The review presents data confirming participation of inflammasomes in the pathogenesis of psoriasis. Much attention is paid to description of pharmacological inhibitors of inflammasomes, which in the future may be the drugs of choice for treatment of inflammatory diseases. The study of molecular mechanisms of the innate immune system will reveal new approaches to prognosis and development of targeted therapy for psoriasis.

врожденный иммунитетпсориазинфламмасомаToll-подобные рецепторывоспалениетаргетная терапияinnate immunitypsoriasisinflammasomeToll-like receptorsinflammationtargeted therapyReferencesБельтюкова А.С., Сысоев К.А., Ильина Т.Н., Шемеровская Т.Г., Хобейш М.М., Монахов К.Н., Тотолян А.А. Экспрессия мРНК хемокинов и хемокиновых рецепторов в коже больных псориазом // Медицинская иммунология, 2008. Т. 10, № 4-5. С. 337-346. doi: 10.15789/1563-0625-2008-4-5-337-346.Beltiukova A.S., Syssoev K.A., Il’ina T.N., Shemerovskaya T.G., Hobeish M.M., Monakhov K.N., Totolian A.A. Expression of mRNAS for chemokines and chemokine receptors in the skin from patients with psoriasis. Meditsinskaya immunologiya = Medical Immunology (Russia), 2008, Vol. 10, no. 4-5, pp. 337-346. (In Russ.) doi: 10.15789/1563-0625-2008-4-5-337-346.Ковальчук Л.В., Ганковская Л.В., Мешкова Р.Я. Клиническая иммунология и аллергология с основами общей иммунологии. М.: ГЭОТАР-Медиа, 2014. 640 c.Kovalchuk L.V., Gankovskaya L.V., Meshkova R.Ya. Clinical immunology and allergology with the basics of general immunology. Moscow: GEOTAR-Media, 2014. 640 р.Меркушова Е.Д., Хасанова Е.М., Свитич О.А., Баткаева Н.В., Гитинова М.М., Ганковская Л.В. Роль TLR9 и компонентов инфламмасомного комплекса в иммунопатогенезе псориаза // Российский иммунологический журнал, 2019. Т. 13 (22), № 2. С. 406-408.Merkushova E.D., Khasanova E.M., Switich О.А., Batkaeva N.V., Gitinova M.M., Gankovskaya L.V. The role of TLR9 and components of the inflammasoma complex in immunopathogenesis of psoriasis. Rossiyskiy immunologicheskiy zhurnal = Russian Journal of Immunology, 2019, Vol. 13, no. 22, pp. 406-408. (In Russ.)Молочков В.А., Бадокин В.В., Альбанова В.И., Волнухин В.А. Псориаз и псориатический артрит. М.: Т-во научных изданий КМК; Авторская академия, 2007. 298 с.Molochkov V.A., Badokin V.V., Albanova V.I., Volnukhin V.A. Psoriasis and psoriatic arthritis. Moscow: KMK Scientific Press; Author’s Academy. 2007. 298 p.Смирнова С.В., Смольникова М.В. Иммунопатогенез псориаза и псориатического артрита // Медицинская иммунология, 2014. Т. 16, № 2. С. 127-138. doi: 10.15789/1563-0625-2014-2-127-138.Smirnova S.V., Smolnikova M.V. Immune pathogenesis of psoriasis and psoriatic arthritis. Meditsinskaya immunologiya = Medical Immunology (Russia), 2014, Vol. 16, no. 2, pp. 127-138. (In Russ.) doi: 10.15789/1563-0625-2014-2-127-138.Ярилин А.А. Иммунология: учебник. М.: ГОЭТАР-Медиа, 2010. 752 с.Ярилин А.А. Иммунология: учебник. М.: ГОЭТАР-Медиа, 2010. 752 с. [Yarilin A.A. Immunology: textbook]. Moscow: GEOTAR-Media, 2010. 752 p.Anwar M.A., Basith S., Choi S. Negative regulatory approaches to the attenuation of Toll-like receptor signaling. Exp. Mol. Med., 2013, Vol. 45, no. 2, pp. 1-14.Anwar M.A., Basith S., Choi S. Negative regulatory approaches to the attenuation of Toll-like receptor signaling. Exp. Mol. Med., 2013, Vol. 45, no. 2, pp. 1-14.Barrat F.J., Meeker T., Gregorio J., Chan J.H., Uematsu S., Akira S., Chang B., Duramad O., Coffman R.L. Nucleic acids of mammalian origin can act as endogenous ligands for toll-like receptors and may promote systemic lupus erythematosus. J. Exp. Med., 2005, Vol. 202, no. 8, pp. 1131-1139.Barrat F.J., Meeker T., Gregorio J., Chan J.H., Uematsu S., Akira S., Chang B., Duramad O., Coffman R.L. Nucleic acids of mammalian origin can act as endogenous ligands for toll-like receptors and may promote systemic lupus erythematosus. J. Exp. Med., 2005, Vol. 202, no. 8, pp. 1131-1139.Bauernfeind F. Of inflammasomes and pathogens--sensing of microbes by the inflammasome. EMBO Mol. Med., 2013, Vol. 5, no. 6, pp. 14-26.Bauernfeind F. Of inflammasomes and pathogens--sensing of microbes by the inflammasome. EMBO Mol. Med., 2013, Vol. 5, no. 6, pp. 14-26.Bianchi M. DAMPs, PAMPs and alarmins: all we need to know about danger. J. Leukoc. Biol., 2007, Vol. 81, no. 1, pp. 1-5.Bianchi M. DAMPs, PAMPs and alarmins: all we need to know about danger. J. Leukoc. Biol., 2007, Vol. 81, no. 1, pp. 1-5.Boxer M.B., Shen M., Auld D.S., Wells J.A., Thomas C.J. A small molecule inhibitor of Caspase 1. Probe reports from the NIH Molecular Libraries Program. Bethesda, MD: National Center for Biotechnology Information 2010. Available at: https://www.ncbi.nlm.nih.gov/books/NBK56241/.Boxer M.B., Shen M., Auld D.S., Wells J.A., Thomas C.J. A small molecule inhibitor of Caspase 1. Probe reports from the NIH Molecular Libraries Program. Bethesda, MD: National Center for Biotechnology Information 2010. Available at: https://www.ncbi.nlm.nih.gov/books/NBK56241/.Cohen S., Fleischmann R. Kinase inhibitors: a new approach to rheumatoid arthritis treatment. Curr. Opin. Rheumatol., 2010, Vol. 22, no. 2, pp. 330-335.Cohen S., Fleischmann R. Kinase inhibitors: a new approach to rheumatoid arthritis treatment. Curr. Opin. Rheumatol., 2010, Vol. 22, no. 2, pp. 330-335.Curry J.L., Qin J.Z., Bonish B., Carrick R., Bacon P., Panella J., Robinson J., Nickoloff B.J. Innate immunerelated receptors in normal and psoriatic skin. Arch. Pathol. Lab. Med., 2003, Vol. 127, pp. 178-186.Curry J.L., Qin J.Z., Bonish B., Carrick R., Bacon P., Panella J., Robinson J., Nickoloff B.J. Innate immunerelated receptors in normal and psoriatic skin. Arch. Pathol. Lab. Med., 2003, Vol. 127, pp. 178-186.Daniels M.J., Rivers-Auty J., Schilling T., Spencer N.G., Watremez W., Fasolino V., Booth S.J., White C.S., Baldwin A.G., Freeman S., Wong R., Latta C., Yu S., Jackson J., Fischer N., Koziel V., Pillot T., Bagnall J., Allan S.M., Paszek P., Galea J., Harte M.K., Eder C., Lawrence C.B., Brough D. Fenamate NSAIDs inhibit the NLRP3 inflammasome and protect against Alzheimer’s disease in rodent models. Nat. Commun., 2016, Vol. 7, 12504. doi: 10.1038/ncomms12504.Daniels M.J., Rivers-Auty J., Schilling T., Spencer N.G., Watremez W., Fasolino V., Booth S.J., White C.S., Baldwin A.G., Freeman S., Wong R., Latta C., Yu S., Jackson J., Fischer N., Koziel V., Pillot T., Bagnall J., Allan S.M., Paszek P., Galea J., Harte M.K., Eder C., Lawrence C.B., Brough D. Fenamate NSAIDs inhibit the NLRP3 inflammasome and protect against Alzheimer’s disease in rodent models. Nat. Commun., 2016, Vol. 7, 12504. doi: 10.1038/ncomms12504.Darakhshan S., Pour A.B. Tranilast: a review of its therapeutic applications. Pharmacol. Res., 2015, Vol. 91, pp. 15-28.Darakhshan S., Pour A.B. Tranilast: a review of its therapeutic applications. Pharmacol. Res., 2015, Vol. 91, pp. 15-28.di Virgilio F. The therapeutic potential of modifying inflammasomes and NOD-like receptors. Pharmacol. Rev., 2013, Vol. 65, no. 3, pp. 872-905.di Virgilio F. The therapeutic potential of modifying inflammasomes and NOD-like receptors. Pharmacol. Rev., 2013, Vol. 65, no. 3, pp. 872-905.Dombrowski Y., Peric M., Koglin S., Kammerbauer C., Göss C., Anz D. Cytosolic DNA triggers inflammasome activation in keratinocytes in psoriatic lesions. Sci. Transl. Med., 2011, Vol. 3, no. 82, pp. 82ra38.Dombrowski Y., Peric M., Koglin S., Kammerbauer C., Göss C., Anz D. Cytosolic DNA triggers inflammasome activation in keratinocytes in psoriatic lesions. Sci. Transl. Med., 2011, Vol. 3, no. 82, pp. 82ra38.Fischer U., Schulze-Osthoff K. Apoptosis-based therapies and drug targets. Cell Death Differ., 2005, Vol. 12, pp. 942-961.Fischer U., Schulze-Osthoff K. Apoptosis-based therapies and drug targets. Cell Death Differ., 2005, Vol. 12, pp. 942-961.Fritz J.H., Girardin S.E., Fitting C., Werts C., Mengin-Lecreulx D., Caroff M. et al. Synergistic stimulation of human monocytes and dendritic cells by Toll-like receptor 4 and NOD1- and NOD2-activating agonists. Eur. J. Immunol., 2005, Vol. 35, no. 8, pp. 2459-2470.Fritz J.H., Girardin S.E., Fitting C., Werts C., Mengin-Lecreulx D., Caroff M. et al. Synergistic stimulation of human monocytes and dendritic cells by Toll-like receptor 4 and NOD1- and NOD2-activating agonists. Eur. J. Immunol., 2005, Vol. 35, no. 8, pp. 2459-2470.Garshick M.S., Barrett T.J., Wechter T. Inflammasome signaling and impaired vascular health in psoriasis. Arterioscler. Thromb. Vasc. Biol., 2019, Vol. 39, no. 4, pp. 787-798.Garshick M.S., Barrett T.J., Wechter T. Inflammasome signaling and impaired vascular health in psoriasis. Arterioscler. Thromb. Vasc. Biol., 2019, Vol. 39, no. 4, pp. 787-798.Hari A., Flach T.L., Shi Y., Mydlarski P.R. Toll-like receptors: role in dermatological disease. Mediators Inflamm., 2011 Vol. 2010, 437246. doi: 10.1155/2010/437246.Hari A., Flach T.L., Shi Y., Mydlarski P.R. Toll-like receptors: role in dermatological disease. Mediators Inflamm., 2011 Vol. 2010, 437246. doi: 10.1155/2010/437246.He Y., Varadarajan S., Muñoz-Planillo R., Burberry A., Nakamura Y., Núñez G. 3, 4-methylenedioxy-βnitrostyrene inhibits NLRP3 inflammasome activation by blocking assembly of the inflammasome. J. Biol. Chem., 2014, Vol. 289, pp. 1142-1150.He Y., Varadarajan S., Muñoz-Planillo R., Burberry A., Nakamura Y., Núñez G. 3, 4-methylenedioxy-βnitrostyrene inhibits NLRP3 inflammasome activation by blocking assembly of the inflammasome. J. Biol. Chem., 2014, Vol. 289, pp. 1142-1150.Heinrich M., Robles M., West J.E., Ortiz de Montellano B.R., Rodriguez E. Ethnopharmacology of Mexican asteraceae (compositae). Ann. Rev. Pharmacol. Toxicol., 1998, Vol. 38, pp. 539-565.Heinrich M., Robles M., West J.E., Ortiz de Montellano B.R., Rodriguez E. Ethnopharmacology of Mexican asteraceae (compositae). Ann. Rev. Pharmacol. Toxicol., 1998, Vol. 38, pp. 539-565.Huang Y., Jiang H., Chen Y., Wang X., Yang Y., Tao J., Deng X., Liang G., Zhang H., Jiang W., Zhou R. Tranilast directly targets NLRP3 to treat inflammasome-driven diseases. EMBO Mol. Med., 2018, Vol.10, e8689. doi: 10.15252/emmm.201708689.Huang Y., Jiang H., Chen Y., Wang X., Yang Y., Tao J., Deng X., Liang G., Zhang H., Jiang W., Zhou R. Tranilast directly targets NLRP3 to treat inflammasome-driven diseases. EMBO Mol. Med., 2018, Vol.10, e8689. doi: 10.15252/emmm.201708689.Ioannidis I., Ye F., McNally B., Willette M., Flaño E. Toll-like receptor expression and induction of type I and type III interferons in primary airway epithelial cells. J. Virol., 2013, Vol. 87, no. 6, pp. 3261-3270.Ioannidis I., Ye F., McNally B., Willette M., Flaño E. Toll-like receptor expression and induction of type I and type III interferons in primary airway epithelial cells. J. Virol., 2013, Vol. 87, no. 6, pp. 3261-3270.Janeway C.A. Jr., Medzhitov R. Innate immune recognition. Annu. Rev. Immunol., 2002, Vol. 20, pp. 197-216. doi: 10.1146/annurev.immunol.20.083001.084359.Janeway C.A. Jr., Medzhitov R. Innate immune recognition. Annu. Rev. Immunol., 2002, Vol. 20, pp. 197-216. doi: 10.1146/annurev.immunol.20.083001.084359.Juliana C., Fernandes-Alnemri T., Wu J., Datta P., Solorzano L., Yu J.-W., Meng R., Quong A.A., Latz E., Scott C.P., Alnemri E.S. Anti-inflammatory compounds parthenolide and Bay 11-7082 are direct inhibitors of the inflammasome. J. Biol. Chem., 2010, Vol. 285, pp. 9792-9802.Juliana C., Fernandes-Alnemri T., Wu J., Datta P., Solorzano L., Yu J.-W., Meng R., Quong A.A., Latz E., Scott C.P., Alnemri E.S. Anti-inflammatory compounds parthenolide and Bay 11-7082 are direct inhibitors of the inflammasome. J. Biol. Chem., 2010, Vol. 285, pp. 9792-9802.Kamata M., Tada Y. Safety of biologics in psoriasis. J. Dermatol., 2018, Vol. 45, no. 3, pp.279-286.Kamata M., Tada Y. Safety of biologics in psoriasis. J. Dermatol., 2018, Vol. 45, no. 3, pp.279-286.Kuwar R., Rolfe A., Di L., Xu H., He L., Jiang Y. A novel small molecular NLRP3 inflammasome inhibitor alleviates neuroinflammatory response following traumatic brain injury. J. Neuroinflamm., 2019, Vol. 16, 81. doi:10.1186/s12974-019-1471-y.Kuwar R., Rolfe A., Di L., Xu H., He L., Jiang Y. A novel small molecular NLRP3 inflammasome inhibitor alleviates neuroinflammatory response following traumatic brain injury. J. Neuroinflamm., 2019, Vol. 16, 81. doi:10.1186/s12974-019-1471-y.Lai C.Y., Su Y.W., Lin K.I., Hsu L.C., Chuang T.H. Natural modulators of endosomal toll-like receptormediated psoriatic skin inflammation. J. Immunol. Res., 2017, Vol. 2017, 7807313. doi: 10.1155/2017/7807313.Lai C.Y., Su Y.W., Lin K.I., Hsu L.C., Chuang T.H. Natural modulators of endosomal toll-like receptormediated psoriatic skin inflammation. J. Immunol. Res., 2017, Vol. 2017, 7807313. doi: 10.1155/2017/7807313.Lamkanfi M., Mueller J.L., Vitari A.C., Misaghi S., Fedorova A., Deshayes K., Lee W.P., Hoffman H.M., Dixit V.M. Glyburide inhibits the Cryopyrin/Nalp3 inflammasome. J. Cell Biol., 2009, Vol. 187, pp. 61-70.Lamkanfi M., Mueller J.L., Vitari A.C., Misaghi S., Fedorova A., Deshayes K., Lee W.P., Hoffman H.M., Dixit V.M. Glyburide inhibits the Cryopyrin/Nalp3 inflammasome. J. Cell Biol., 2009, Vol. 187, pp. 61-70.Lee C.C., Avalos A.M., Ploegh H.L. Accessory molecules for Toll-like receptors and their function. Nat. Rev. Immunol., 2012, Vol. 12, no. 3, pp. 168-179.Lee C.C., Avalos A.M., Ploegh H.L. Accessory molecules for Toll-like receptors and their function. Nat. Rev. Immunol., 2012, Vol. 12, no. 3, pp. 168-179.Liu X., Zhang Z., Ruan J., Pan Y., Magupalli V.G., Wu H., Lieberman J. Inflammasome-activated gasdermin D causes pyroptosis by forming membrane pores. Nature, 2016, Vol. 535, pp. 153-158.Liu X., Zhang Z., Ruan J., Pan Y., Magupalli V.G., Wu H., Lieberman J. Inflammasome-activated gasdermin D causes pyroptosis by forming membrane pores. Nature, 2016, Vol. 535, pp. 153-158.Lowes M.A., Suárez-Fariñas M., Krueger J.G. Immunology of зsoriasis. Annu. Rev. Immunol., 2014, Vol. 32, pp. 227-255.Lowes M.A., Suárez-Fariñas M., Krueger J.G. Immunology of зsoriasis. Annu. Rev. Immunol., 2014, Vol. 32, pp. 227-255.Mabuchi T., Chang T.W., Quinter S., Hwang S.T. Chemokine receptors in the pathogenesis and therapy of psoriasis. J. Dermatol. Sci., 2012, Vol. 65, Iss. 1, pp. 4-11.Mabuchi T., Chang T.W., Quinter S., Hwang S.T. Chemokine receptors in the pathogenesis and therapy of psoriasis. J. Dermatol. Sci., 2012, Vol. 65, Iss. 1, pp. 4-11.Marchetti C., Swartzwelter B., Gamboni F., Neff C.P., Richter K., Azam T., Carta S., Tengesdal I., Nemkov T., d’Alessandro A., Henry C., Jones G.S., Goodrich S.A., St. Laurent J.P., Jones T.M., Scribner C.L., Barrow R.B., Altman R.D., Skouras D.B., Gattorno M., Grau V., Janciauskiene S., Rubartelli A., Joosten L.A.B., Dinarello C.A. OLT1177, a β-sulfonyl nitrile compound, safe in humans, inhibits the NLRP3 inflammasome and reverses the metabolic cost of inflammation. Proc. Natl. Acad. Sci. USA, 2018, Vol. 115, pp. 1530-1539.Marchetti C., Swartzwelter B., Gamboni F., Neff C.P., Richter K., Azam T., Carta S., Tengesdal I., Nemkov T., d’Alessandro A., Henry C., Jones G.S., Goodrich S.A., St. Laurent J.P., Jones T.M., Scribner C.L., Barrow R.B., Altman R.D., Skouras D.B., Gattorno M., Grau V., Janciauskiene S., Rubartelli A., Joosten L.A.B., Dinarello C.A. OLT1177, a β-sulfonyl nitrile compound, safe in humans, inhibits the NLRP3 inflammasome and reverses the metabolic cost of inflammation. Proc. Natl. Acad. Sci. USA, 2018, Vol. 115, pp. 1530-1539.Medzhitov R. TLR-mediated innate immune recognition. Semin. Immunol., 2007, Vol. 19, no. 1, pp. 1-2.Medzhitov R. TLR-mediated innate immune recognition. Semin. Immunol., 2007, Vol. 19, no. 1, pp. 1-2.Miller L.S. Toll-like receptors in skin. Adv. Dermatol., 2008, Vol. 24, pp. 71-87.Miller L.S. Toll-like receptors in skin. Adv. Dermatol., 2008, Vol. 24, pp. 71-87.Mullen L.M., Chamberlain G., Sacre S. Pattern recognition receptors as potential therapeutic targets in inflammatory rheumatic disease. Arthritis Res. Ther., 2015, Vol. 17, no. 1, 122. doi: 10.1186/s13075-015-0645-y.Mullen L.M., Chamberlain G., Sacre S. Pattern recognition receptors as potential therapeutic targets in inflammatory rheumatic disease. Arthritis Res. Ther., 2015, Vol. 17, no. 1, 122. doi: 10.1186/s13075-015-0645-y.Nair R.P., Henseler T., Jenisch S., Stuart P., Bichakjian C.K., Lenk W., Westphal E., Guo S.W., Christophers E., Voorhees J.J., Elder J.T. Evidence for two psoriasis susceptibility loci (HLA and 17q) and two novel candidate regions (16q and 20p) by genome-wide scan. Hum. Mol. Genet., 1997, Vol. 6, no. 8, pp. 1349-1356.Nair R.P., Henseler T., Jenisch S., Stuart P., Bichakjian C.K., Lenk W., Westphal E., Guo S.W., Christophers E., Voorhees J.J., Elder J.T. Evidence for two psoriasis susceptibility loci (HLA and 17q) and two novel candidate regions (16q and 20p) by genome-wide scan. Hum. Mol. Genet., 1997, Vol. 6, no. 8, pp. 1349-1356.Oviedo-Boyso J., Bravo-Patiño A., Baizabal-Aguirre V.M. Collaborative action of toll-like and nod-like receptors as modulators of the inflammatory response to pathogenic bacteria. Mediators Inflamm., 2014, Vol. 2014, 432785. doi: 10.1155/2014/432785.Oviedo-Boyso J., Bravo-Patiño A., Baizabal-Aguirre V.M. Collaborative action of toll-like and nod-like receptors as modulators of the inflammatory response to pathogenic bacteria. Mediators Inflamm., 2014, Vol. 2014, 432785. doi: 10.1155/2014/432785.Perregaux D.G., McNiff P., Laliberte R., Hawryluk N., Peurano H., Stam E., Eggler J., Griffiths R., Dombroski M.A., Gabel C.A. Identification and characterization of a novel class of interleukin-1 post-translational processing inhibitors. J. Pharmacol. Exp. Ther., 2001, Vol. 299, pp. 187-197.Perregaux D.G., McNiff P., Laliberte R., Hawryluk N., Peurano H., Stam E., Eggler J., Griffiths R., Dombroski M.A., Gabel C.A. Identification and characterization of a novel class of interleukin-1 post-translational processing inhibitors. J. Pharmacol. Exp. Ther., 2001, Vol. 299, pp. 187-197.Platten M., Ho P.P., Youssef S., Fontoura P., Garren H., Hur E.M., Gupta R., Lee L.Y., Kidd B.A., Robinson W.H., Sobel R.A., Selley M.L., Steinman L. Treatment of autoimmune neuroinflammation with a synthetic tryptophan metabolite. Science, 2005, Vol. 310, pp. 850-855.Platten M., Ho P.P., Youssef S., Fontoura P., Garren H., Hur E.M., Gupta R., Lee L.Y., Kidd B.A., Robinson W.H., Sobel R.A., Selley M.L., Steinman L. Treatment of autoimmune neuroinflammation with a synthetic tryptophan metabolite. Science, 2005, Vol. 310, pp. 850-855.Reinholz M., Ruzicka T., Schauber J. Cathelicidin LL-37: an antimicrobial peptide with a role in inflammatory skin disease. Ann. Dermatol., 2012, Vol. 24, no. 2, pp. 126-135.Reinholz M., Ruzicka T., Schauber J. Cathelicidin LL-37: an antimicrobial peptide with a role in inflammatory skin disease. Ann. Dermatol., 2012, Vol. 24, no. 2, pp. 126-135.Riddle M.C. Editorial: sulfonylureas differ in effects on ischemic preconditioning–is it time to retire glyburide? J. Clin. Endocrinol. Metab., 2003, Vol. 88, pp. 528-530.Riddle M.C. Editorial: sulfonylureas differ in effects on ischemic preconditioning–is it time to retire glyburide? J. Clin. Endocrinol. Metab., 2003, Vol. 88, pp. 528-530.Rudolphi K., Gerwin N., Verzijl N., Kraan P.V.D., Berg W.V.D. Pralnacasan, an inhibitor of interleukin-1β converting enzyme, reduces joint damage in two murine models of osteoarthritis. Osteoarthritis Cartilage, 2003, Vol. 11, pp. 738-746.Rudolphi K., Gerwin N., Verzijl N., Kraan P.V.D., Berg W.V.D. Pralnacasan, an inhibitor of interleukin-1β converting enzyme, reduces joint damage in two murine models of osteoarthritis. Osteoarthritis Cartilage, 2003, Vol. 11, pp. 738-746.Saïd-Sadier N., Ojcius D.M. Alarmins, inflammasomes and immunity. Biomed. J., 2012, Vol. 35, no. 6, pp. 437-449.Saïd-Sadier N., Ojcius D.M. Alarmins, inflammasomes and immunity. Biomed. J., 2012, Vol. 35, no. 6, pp. 437-449.Salskov-Iversen M.L., Johansen C., Kragballe K., Iversen L. Caspase-5 expression is upregulated in lesional psoriatic skin. J. Invest. Dermatol., 2011, Vol. 131, pp. 670-676.Salskov-Iversen M.L., Johansen C., Kragballe K., Iversen L. Caspase-5 expression is upregulated in lesional psoriatic skin. J. Invest. Dermatol., 2011, Vol. 131, pp. 670-676.Siegmund B., Zeitz M. Pralnacasan (vertex pharmaceuticals). IDrugs, 2003, Vol. 6, pp. 154-158.Siegmund B., Zeitz M. Pralnacasan (vertex pharmaceuticals). IDrugs, 2003, Vol. 6, pp. 154-158.Su F., Xia Y., Huang M., Zhang L., Chen L. Expression of NLPR3 in Psoriasis is associated with enhancement of interleukin-1β and caspase-1. Med. Sci. Monit., 2018, Vol. 24, pp. 7909-7913.Su F., Xia Y., Huang M., Zhang L., Chen L. Expression of NLPR3 in Psoriasis is associated with enhancement of interleukin-1β and caspase-1. Med. Sci. Monit., 2018, Vol. 24, pp. 7909-7913.Takagi M., Takakubo Y., Pajarinen J., Naganuma Y., Oki H., Maruyama M., Goodman S.B. Danger of frustrated sensors: Role of Toll-like receptors and NOD-like receptors in aseptic and septic inflammations around total hip replacements. J. Orthop. Translat., 2017, Vol. 10, pp. 68-85.Takagi M., Takakubo Y., Pajarinen J., Naganuma Y., Oki H., Maruyama M., Goodman S.B. Danger of frustrated sensors: Role of Toll-like receptors and NOD-like receptors in aseptic and septic inflammations around total hip replacements. J. Orthop. Translat., 2017, Vol. 10, pp. 68-85.Takeuchi O., Akira S. Pattern recognition receptors and inflammation. Cell, 2010, Vol. 140, Iss. 6, pp. 805-820.Takeuchi O., Akira S. Pattern recognition receptors and inflammation. Cell, 2010, Vol. 140, Iss. 6, pp. 805-820.Telfer N.R., Chalmers R.J., Whale K., Colman G. The role of streptococcal infection in the initiation of guttate psoriasis. Arch. Dermatol., 1992, Vol. 128, no. 1, pp. 39-42.Telfer N.R., Chalmers R.J., Whale K., Colman G. The role of streptococcal infection in the initiation of guttate psoriasis. Arch. Dermatol., 1992, Vol. 128, no. 1, pp. 39-42.Toldo S., Abbate A. The NLRP3 inflammasome in acute myocardial infarction. Nat. Rev. Cardiol., 2018, Vol. 15, pp. 203-214.Toldo S., Abbate A. The NLRP3 inflammasome in acute myocardial infarction. Nat. Rev. Cardiol., 2018, Vol. 15, pp. 203-214.Tonel G., Conrad C. Interplay between keratinocytes and immune cells-recent insights into psoriasis pathogenesis. Int. J. Biochem. Cell Biol., 2009, Vol. 41, no. 5, pp. 963-968.Tonel G., Conrad C. Interplay between keratinocytes and immune cells-recent insights into psoriasis pathogenesis. Int. J. Biochem. Cell Biol., 2009, Vol. 41, no. 5, pp. 963-968.Visscher P., Wray N., Zhang Q., Sklar P., McCarthy M., Brown M., Yang J.10 years of GWAS discovery: biology, function, and translation. Am. J. Hum. Genet., 2017, Vol. 101, pp. 5-22.Visscher P., Wray N., Zhang Q., Sklar P., McCarthy M., Brown M., Yang J.10 years of GWAS discovery: biology, function, and translation. Am. J. Hum. Genet., 2017, Vol. 101, pp. 5-22.Wannamaker W., Davies R., Namchuk M., Pollard J., Ford P., Ku G., Decker C., Charifson P., Weber P., Germann U.A., Kuida K., Randle J.C. (S)-1-((S)-2-{[1-(4-Amino-3-chloro-phenyl)-methanoyl]-amino}-3,3-dimethylbutanoyl)-pyrrolidine-2-carboxylic acid ((2R,3S)-2-ethoxy-5-oxo-tetrahydro-furan-3-yl)-amide (VX-765), an Orally Available Selective Interleukin (IL)-Converting Enzyme/Caspase-1 Inhi. J. Pharmacol. Exp. Ther., 2007, Vol. 321, pp. 509-516.Wannamaker W., Davies R., Namchuk M., Pollard J., Ford P., Ku G., Decker C., Charifson P., Weber P., Germann U.A., Kuida K., Randle J.C. (S)-1-((S)-2-{[1-(4-Amino-3-chloro-phenyl)-methanoyl]-amino}-3,3-dimethylbutanoyl)-pyrrolidine-2-carboxylic acid ((2R,3S)-2-ethoxy-5-oxo-tetrahydro-furan-3-yl)-amide (VX-765), an Orally Available Selective Interleukin (IL)-Converting Enzyme/Caspase-1 Inhi. J. Pharmacol. Exp. Ther., 2007, Vol. 321, pp. 509-516.Williams A., Flavell R.A., Eisenbarth S.C. The role of NOD-like Receptors in shaping adaptive immunity. Curr. Opin. Immunol., 2010, Vol. 22, no. 1, pp. 34-40.Williams A., Flavell R.A., Eisenbarth S.C. The role of NOD-like Receptors in shaping adaptive immunity. Curr. Opin. Immunol., 2010, Vol. 22, no. 1, pp. 34-40.Xiao J., Wang C., Yao J.C., Alippe Y., Xu C., Kress D., Civitelli R., Abu-Amer Y., Kanneganti T.D., Link D.C., Mbalaviele G. Gasdermin D mediates the pathogenesis of neonatal-onset multisystem inflammatory disease in mice. Plos Biol., 2018, Vol. 16, no. 11, e3000047. doi: 10.1371/journal.pbio.3000047.Xiao J., Wang C., Yao J.C., Alippe Y., Xu C., Kress D., Civitelli R., Abu-Amer Y., Kanneganti T.D., Link D.C., Mbalaviele G. Gasdermin D mediates the pathogenesis of neonatal-onset multisystem inflammatory disease in mice. Plos Biol., 2018, Vol. 16, no. 11, e3000047. doi: 10.1371/journal.pbio.3000047.Yamaoka K., Tanaka Y. Jak inhibitor; possibility and mechanism as a new disease modifying anti-rheumatic drug. Jpn J. Clin. Immunology, 2009, Vol. 32, no. 2, pp. 85-91.Yamaoka K., Tanaka Y. Jak inhibitor; possibility and mechanism as a new disease modifying anti-rheumatic drug. Jpn J. Clin. Immunology, 2009, Vol. 32, no. 2, pp. 85-91.Youm Y.-H., Nguyen K.Y., Grant R.W., Goldberg E.L., Bodogai M., Kim D., d’Agostino D., Planavsky N., Lupfer C., Kanneganti T.D., Kang S., Horvath T.L., Fahmy T.M., Crawford P.A., Biragyn A., Alnemri E., Dixit V.D. The ketone metabolite β-hydroxybutyrate blocks NLRP3 inflammasome–mediated inflammatory disease. Nat. Med., 2015, Vol. 21, pp. 263-269.Youm Y.-H., Nguyen K.Y., Grant R.W., Goldberg E.L., Bodogai M., Kim D., d’Agostino D., Planavsky N., Lupfer C., Kanneganti T.D., Kang S., Horvath T.L., Fahmy T.M., Crawford P.A., Biragyn A., Alnemri E., Dixit V.D. The ketone metabolite β-hydroxybutyrate blocks NLRP3 inflammasome–mediated inflammatory disease. Nat. Med., 2015, Vol. 21, pp. 263-269.

The authors declare that there are no conflicts of interest present.