Инфламмасома как ранний патофизиологический феномен воспалительного процесса при болезнях кожи и других патологиях

В обзоре рассмотрены молекулярная структура, последовательность, пути активации инфламмасом, варианты нисходящих эффектов и их связь с аутовоспалительными, аутоиммунными, нейродегенеративными, аллергическими и злокачественными патологиями, с фокусом на вовлечение кожи в патологический процесс. Дана интерпретация инфламмасом как раннего патофизиологического события перед началом воспалительного процесса и возможные варианты нарушения регуляции их функционирования. Более подробно описаны все аспекты исследований, относящихся к инфламмасоме NLRP3. Приведены данные по имеющимся и перспективным направлениям терапевтических интервенций при NLRP3-ассоциированных болезнях.

1. Lara-Reyna S., Caseley E.A., Topping J., Rodrigues F., Jimenez Macias J., Lawler S.E. et al. Inflammasome activation: from molecular mechanisms to autoinflammation. Clin. Transl. Immunol. 2022;11(7):e1404. DOI: 10.1002/cti2.1404.

2. Tang L., Zhou F. Inflammasomes in common immune-related skin diseases. Front. Immunol. 2020;11:882. DOI: 10.3389/fimmu.2020.00882.

3. Klimov V.V. Innate immunity. In: From basic to clinical immunology. Cham: Springer, 2019:127–159. DOI: 10.1007/978-3-030-03323-1_3.

4. Danis J., Mellett M. Nod-Like receptors in host defence and disease at the epidermal barrier. Int. J. Mol. Sci. 2021;22(9):4677. DOI: 10.3390/ijms22094677.

5. Jacquet A. Characterization of innate immune responses to house dust mite allergens: Pitfalls and limitations. Front. Allergy. 2021;2:662378. DOI: 10.3389/falgy.2021.662378.

6. Liu B., Li A., Xu J., Cui Y. Single-cell transcriptional analysis deciphers the inflammatory response of skin-resident stromal cells. Front. Surg. 2022;9:935107. DOI: 10.3389/fsurg.2022.935107.

7. Solé-Boldo L., Raddatz G., Schütz S., Mallm J.-P., Rippe K., Lonsdorf A.S. et al. Single-cell transcriptomes of the human skin reveal age-related loss of fibroblast priming. Commun. Biol. 2020;3(1):188. DOI: 10.1038/s42003-020-0922-4.

8. Nagar A., Rahman T., Harton J.A. The ASC Speck and NLRP3 inflammasome function are spatially and temporally distinct. Front. Immunol. 2021;12:752482. DOI: 10.3389/fimmu.2021.752482.

9. Ciążyńska A., Bednarski I.A., Wódz K., Narbutt J., Lesiak A. NLRP1 and NLRP3 inflammasomes as a new approach to skin carcinogenesis (Review). Oncol. Letters. 2020;19(3):1649– 1656. DOI: 10.3892/ol.2020.11284.

10. Ross C., Chan A.H., von Pein J.B., Maddugoda M.P., Boucher D., Schroder K. Inflammatory caspases: toward a unified model for caspase activation by inflammasomes. Annu. Rev. Immunol. 2022;40:249–269. DOI: 10.1146/annurev-immunol-101220-030653.

11. Lillo S., Saleh M. Inflammasomes in cancer progression and anti-tumor immunity. Front. Cell Dev. Biol. 2022;10:839041. DOI: 10.3389/fcell.2022.839041.

12. Martinon F., Burns K., Tschopp J. The inflammasome: a molecular platform triggering activation of inflammatory caspase and processing of proIL-beta. Mol. Cell. 2002;10(2):417–426. DOI: 10.1016/s1097-2765(02)00599-3.

13. Tsang M.S.-M., Hou T., Chan B.C.-L., Wong C.K. Immunological roles of NLR in allergic diseases and its underlying mechanisms. Int. J. Mol. Sci. 2021;22(4):1507. DOI: 10.3390/ijms22041507.

14. Lachner J., Mlitz V., Tschachler E., Eckhart L. Epidermal cornification is preceded by the expression of a keratinocyte-specific set of pyroptosis-related genes. Sci. Rep. 2017;7(1):17446. DOI: 10.1038/s41598-017-17782-4.

15. Samir P., Malireddi R.K.S., Kanneganti T.D. The PANoptosome: A deadly protein complex driving pyroptosis, apoptosis, and necroptosis (PANoptosis). Front. Cell Infect. Microbiol. 2020;10:238. DOI: 10.3389/fcimb.2020.00238.

16. Дмитриев Ю.В., Галагудза М.М. Некроптоз и опыт его таргетной модуляции в контексте персонализированной медицины. Российский журнал персональной медицины. 2022;2(2):33–45. DOI: 10.18705/2782-3806-2022-2-2-33-45.

17. Li Y., Sun L., Zhang Y. Programmed cell death in the epithelial cells of the nasal mucosa in allergic rhinitis. Int. Immunopharm. 2022;112:109252. DOI: 10.1016/j.intimp.2022.109252.

18. Swanson K.V., Deng M., Ting J.P. The NLRP3 inflammasome: molecular activation and regulation to therapeutics. Nat. Rev. Immunol. 2019;19(8):477–489. DOI: 10.1038/s41577-019-0165-0.

19. Seok J.K., Kang H.C., Cho Y.Y., Lee H.S., Lee J.Y. Regulation of the NLRP3 inflammasome by post-translational modifications and small molecules. Front. Immunol. 2020;11:618231. DOI: 10.3389/fimmu.2020.618231.

20. Zheng D., Liwinski T., Elinav E. Inflammasome activation and regulation: toward a better understanding of complex mechanisms. Cell Discov. 2020;6(1):36. DOI: 10.1038/s41421-020-0167-x.

21. Zheng J., Yao L., Zhou Y., Gu X., Wang C., Bao K. et al. A novel function of NLRP3 independent of inflammasome as a key transcription factor of IL-33 in epithelial cells of atopic dermatitis. Cell Death Dis. 2021;12(10):871. DOI: 10.1038/s41419-021-04159-9.

22. Fernandez-Duran I., Quintanilla A., Tarrats N., Birch J., Hari P., Millar F.R. et al. Cytoplasmic innate immune sensing by the caspase-4 non-canonical inflammasome promotes cellular senescence. Cell Death Differ. 2022;29(6):1267–1282. DOI: 10.1038/s41418-021-00917-6.

23. Seok J.K., Kang H.C., Cho Y.-Y., Lee H.-S., Lee J.Y. Therapeutic regulation of the NLRP3 inflammasome in chronic inflammatory diseases. Arch. Pharm. Res. 2021;44(1):16–35. DOI: 10.1007/s12272-021-01307-9.

24. Ha H.J., Chun H.L., Lee S.Y., Park H.H. Molecular basis of IRGB10 oligomerization and membrane association for pathogen membrane disruption. Commun. Biol. 2021;4(1):92. DOI: 10.1038/s42003-020-01640-7.

25. Gaidt M.M., Hornung V. Alternative inflammasome activation enables IL-1β release from living cells. Curr. Opin. Immunol. 2017;44:7–13. DOI: 10.1016/j.coi.2016.10.007.

26. Christgen S., David E., Place D.E., Kanneganti T.-D. Toward targeting inflammasomes: Insights into their regulation and activation. Cell Res. 2020;30(4):315–327. DOI: 10.1038/s41422-020-0295-8.

27. Anderton H., Alqudah S. Cell death in skin function, inflammation, and disease. Biochem. J. 2022;479(15):1621–1651. DOI: 10.1042/BCJ20210606.

28. Bertheloot D., Latz E., Franklin B.S. Necroptosis, pyroptosis and apoptosis: An intricate game of cell death. Cell Mol. Immunol. 2021;18(5):1106–1121. DOI: 10.1038/s41423-020-00630-3.

29. Riwaldt S., Corydon T.J., Pantalone D., Sahana J., Wise P., Wehland M. et al. Role of apoptosis in wound healing and apoptosis alterations in microgravity. Front. Bioengin. Biotechnol. 2021;9:679650. DOI: 10.3389/fbioe.2021.679650.

30. Gruber J.V., Holtz R. In vitro expression of NLRP inflammasome-induced active Caspase-1 expression in normal human epidermal keratinocytes (NHEK) by various exogenous threats and subsequent inhibition by naturally derived ingredient blends. J. Inflam. Res. 2019;12:219–230. DOI: 10.2147/JIR.S215776.

31. Buscetta M., Di Vincenzo S., Miele M., Badami E., Pace E., Cipollina C. Cigarette smoke inhibits the NLRP3 inflammasome and leads to caspase-1 activation via the TLR4- TRIF-caspase-8 axis in human macrophages. FASEB J. 2020;34(1):1819–1832. DOI: 10.1096/fj.201901239R.

32. Fenini G., Grossi S., Contassot E., Biedermann T., Reichmann E., French L.E. et al. Genome editing of human primary keratinocytes by CRISPR/Cas9 reveals an essential role of the NLRP1 inflammasome in UVB sensing. J. Invest. Dermatol. 2018;138(12):2644–2652. DOI: 10.1016/j.jid.2018.07.016.

33. Burian M., Yazdi A.S. NLRP1 Is the key inflammasome in primary human keratinocytes. J. Invest. Dermatol. 2018;138(12):2507–2510. DOI: 10.1016/j.jid.2018.08.004.

34. Latz E., Duewell P. NLRP3 inflammasome activation in inflammaging. Sem. Immunol. 2018;40:61–73. DOI: 10.1016/j.smim.2018.09.001.

35. Nardini C., Moreau J.-F., Gensous N., Ravaioli F., Garagnani P., Bacalini M.G. The epigenetics of inflammaging: The contribution of age-related heterochromatin loss and locus-specific remodelling and the modulation by environmental stimuli. Sem. Immunol. 2018;40:49–60. DOI: 10.1016/j.smim.2018.10.009.

36. Cyr B., Hadad R., Keane R.W., Vaccari J.P.R. The role of non-canonical and canonical inflammasomes in inflammaaging. Front. Mol. Neurosci. 2022;15:774014. DOI: 10.3389/fnmol.2022.774014.

37. Ferrara F., Prieux R., Woodby B., Valacchi G. Inflammasome activation in pollution-induced skin conditions. Plast. Reconstr. Surg. 2021;147(1S-2):15S–24S. DOI: 10.1097/PRS.0000000000007617.

38. Georgin-Lavialle S., Fayand A., Rodrigues F., Bachmeyer C., Savey L., Grateau G. Autoinflammatory diseases: state of the art. Presse Med. 2019;48(1Pt2):e25–e48. DOI: 10.1016/j.lpm.2018.12.003.

39. Georgin-Lavialle S., Ducharme-Benard S., Sarrabay G., Savey L., Grateau G., Hentgen V. Systemic autoinflammatory diseases: clinical state of the art. Best practice and research. Clin. Rheumatology. 2020;34(4):101529. DOI: ff10.1016/j.berh.2020.101529.

40. Пирожков С.В., Литвицкий П.Ф. Инфламмасомные болезни. Иммунология. 2018;39(2-3):158–165. DOI: 10.18821/0206-4952-2018-39-2-3-158-165.

41. Zhang Y., Yang W., Li W., Zhao Y. NLRP3 inflammasome: Checkpoint connecting innate and adaptive immunity in autoimmune diseases. Front. Immunol. 2021;12:732933. DOI: 10.3389/fimmu.2021.732933.

42. Wang D., Duncan B., Li X., Shi J. The role of NLRP3 inflammasome in infection-related, immune-mediated and autoimmune skin diseases. J. Dermatol. Sci. 2020;98(3):146–151. DOI: 10.1016/j.jdermsci.2020.03.001.

43. Казимирский А.Н., Салмаси Ж.М., Порядин Г.В., Свитич О.А., Брагвадзе Б.Г., Алексеева А.А., Ганковская Л.В. Роль эпителиальных клеток в патогенезе атопии. Бюллетень сибирской медицины. 2019;8(1):201–210. DOI: 10.20538/1682-0363-2019-1-201-210.

44. Загрешенко Д.С., Климов В.В., Трофименко Н.А., Дорофеева М.С. Интерлейкин-1Β и интерлейкин-18 в экссудатах «кожного окна» у больных хронической крапивницей. Медицина в Кузбассе. 2022;21(3):27–29. DOI: 10.24412/2687-0053-2022-3-27-29.

45. Di Filippo M., Hennig P., Karakaya T., Slaufova M., Beer H.-D. NLRP1 in cutaneous SCCs: An example of the complex roles of inflammasomes in cancer development. Int. J. Mol. Sci. 2022;23(20):12308. DOI: 10.3390/ijms232012308.

46. Zhong F.L., Mamaï O., Sborgi L., Boussofara L., Hopkins R., Robinson K. et al. Germline NLRP1 mutations cause skin inflammatory and cancer susceptibility syndromes via inflammasome activation. Cell. 2016;167(1):187–202.e17. DOI: 10.1016/j.cell.2016.09.001.

47. Thürmann L., Grützmann K., Klös M., Bieg M., Winter M., Polte T. et al. Early-onset childhood atopic dermatitis is related to NLRP2 repression. J. Allergy Clin. Immunol. 2018;141(4):1482–1485.e16. DOI: 10.1016/j.jaci.2017.11.018.

48. Li S., Kang P., Zhang W., Jian Z., Zhang Q., Yi X. et al. Activated NLR family pyrin domain containing 3 (NLRP3) inflammasome in keratinocytes promotes cutaneous T-cell response in patients with vitiligo. J. Allergy Clin. Immunol. 2020;145(2):632–645. DOI: 10.1016/j.jaci.2019.10.036.

49. Deepti V., Shora Z.F., Gunnthorunn S., Cecilia B.E., Charlotta S., Charlotta E. Enhanced inflammasome activity in patients with psoriasis promotes systemic inflammation. J. Invest. Dermatol. 2021;141(3):586–595.e5. DOI: 10.1016/j.jid.2020.07.012.

50. Su F., Xia Y., Huang M., Zhang L., Chen L. Expression of NLPR3 in psoriasis is associated with enhancement of interleukin-1b and caspase-1. Med. Sci. Monit. 2018;24:7909– 7913. DOI: 10.12659/MSM.911347.

51. Tsuji G., Hashimoto-Hachiya A., Yen V.H., Takemura M., Yumine A., Furue K. et al. Metformin inhibits IL-1β secretion via impairment of NLRP3 inflammasome in keratinocytes: implications for preventing the development of psoriasis. Cell Death Discovery. 2020;6:11. DOI: 10.1038/s41420-020-0245-8.

52. Yang B.-Y., Cheng Y.-G., Liu Y., Liu Y., Tan J.-Y., Guan W. et al. Datura Metel L. ameliorates imiquimod-induced psoriasis-like dermatitis and inhibits inflammatory cytokines production through TLR7/8–MyD88–NF-kB–NLRP3 inflammasome pathway. Molecules. 2019;24(11):2157. DOI: 10.3390/molecules24112157.

53. Bonnekoh H., Vera C., Abad‐Perez A., Radetzki S., Neuenschwander M., Specker E. et al. Topical inflammasome inhibition with disulfiram prevents irritant contact dermatitis. Clin. Transl. Allergy. 2021;11(5):e12045. DOI: 10.1002/clt2.12045.

54. Luo Q., Zeng J., Li W., Lin L., Zhou X., Tian X. et al. Silencing of miR155 suppresses inflammatory responses in psoriasis through inflammasome NLRP3 regulation. Int. J. Mol. Med. 2018;42(2):1086–1095. DOI: 10.3892/ijmm.2018.3677.

55. Cai H., Yan L., Liu N., Xu M., Cai H. IFI16 promotes cervical cancer progression by upregulating PD-L1 in immunomicroenvironment through STING-TBK1-NF-kB pathway. Biomed. Pharmacother. 2020;123:109790. DOI: 10.1016/j.biopha.2019.109790.

56. Yang Z., Liang C., Wang T., Zou Q., Zhou M., Cheng Y. et al. Biochem. Biophys. Res. Commun. 2020;522(1):61–67. DOI: 10.1016/j.bbrc.2019.11.031.

57. Kim H., Kim H., Feng Y., Li Y., Tamiya H., Tocci S. et al. PRMT5 control of cGAS/STING and NLRC5 pathways defines melanoma response to antitumor immunity. Sci. Transl. Med. 2020;12(551):eaaz5683. DOI: 10.1126/scitranslmed.aaz5683.

58. Zhou H., Zhang W., Qin D., Liu P., Fan W., Lv H. et al. Activation of NLRP3 inflammasome contributes to the inflammatory response to allergic rhinitis via macrophage pyroptosis. Int. Immunopharmacol. 2022;110:109012. DOI: 10.1016/j.intimp.2022.109012.

59. Pan P., Shen M., Yu Z., Ge W., Chen K., Tian M. et al. SARSCoV-2 N protein promotes NLRP3 inflammasome activation to induce hyperinflammation. Nat. Commun. 2021;12(1):4664. DOI: 10.1038/S41467-021-25015-6.

60. Huang Y., Jiang H., Chen Y., Wang X., Yang Y., Tao J. et al. Tranilast directly targets NLRP3 to treat inflammasome-driven diseases. EMBO Mol. Med. 2018;10(4):e8689. DOI: 10.15252/emmm.201708689.

61. Насонов Е.Л. Роль интерлейкина 1 в развитии заболеваний человека. Научно-практическая ревматология. 2018;56(Прил.4):19–27. DOI: 10.14412/1995-4484-2018-19-27.

62. Skendros P., Papagoras C., Lefaki I., Giatromanolaki A., Kotsianidis I., Speletas M. et al. Successful response in a case of severe pustular psoriasis after interleukin-1beta inhibition. Br. J. Dermatol. 2017;176(1):212–215. DOI: 10.1111/bjd.14685.

63. Sebastian-Valverde M., Wu H., Rahim M.A, Sanchez R., Kumar K., De Vita R.J. et al. Discovery and characterization of small-molecule inhibitors of NLRP3 and NLRC4 inflammasomes. J. Biol. Chem. 2021;296:100597. DOI: 10.1016/j.jbc.2021.100597.

64. Elizagaray M.L., Gomes M.T.R., Guimaraes E.S., Rumbo M., Hozbor D.F., Oliveira S.C. et al. Canonical and non-canonical inflammasome activation by outer membrane vesicles derived from Bordetella pertussis. Front. Immunol. 2020;11:1879. DOI: 10.3389/fimmu.2020.01879.

65. Leszczyńska K., Jakubczyk D., Górska S. The NLRP3 inflammasome as a new target in respiratory disorders treatment. Front. Immunol. 2022;13:1006654. DOI: 10.3389/fimmu.2022.1006654.