The importance of cytokines for the atopic dermatitis pathogenesis
https://doi.org/10.21508/1027-4065-2018-63-1-28-33
Abstract
The atopic dermatitis is a chronic inflammatory skin disease. The wide disease prevalence, increase in a number of the severe forms determine its high medical and social importance. The development of the dermatic inflammatory process in the patients is caused by the complex interaction of the genetic mechanisms, environmental factors, infectious agents, defects of the skin barrier and immunologic mechanisms. The various populations of the immunocompetent cells takes participation in the atopic dermatitis immunopathogenesis: Th1, Th2, Th9, Тh17, Th22, regulatory T-cells and cytokines secreted by them. This review states the data on the participation of a number of cytokines in the development of the immunopathological process in the presence of the atopic dermatitis. The revealing of the particularities of the disease pathogenesis based on the cytokine profile assessment and determination of the clinical course severity markers are the most relevant line of the clinical allergology and immunology for determination not only the disease prognosis but for the therapeutic targets in future as well.
About the Authors
E. E. Varlamov
Research Clinical Institute of Pediatry named after Academician Yu.E. Veltishchev, National Research Medical University named after N.I. Pirogov, Moscow
Russian Federation
Russian Federation
A. N. Pampura
Research Clinical Institute of Pediatry named after Academician Yu.E. Veltishchev, National Research Medical University named after N.I. Pirogov, Moscow
Russian Federation
Russian Federation
V. S. Sukhorukov
Research Clinical Institute of Pediatry named after Academician Yu.E. Veltishchev, National Research Medical University named after N.I. Pirogov, Moscow
Russian Federation
Russian Federation
References
1. Al’banova V.I., Pampura A.N. Atopic dermatitis. Moscow: GEOTAR-Media 2014; 160. (in Russ)
2. Elisjutina O.G., Fedenko E.S., Boldyreva M.N., Gudima G.O. Features of immune response and the role of some cytokines in atopic dermatitis. Ros allergol zhurn 2015; 1: 3–14. (in Russ)
3. Bieber Th. Atopic dermatitis 2.0: from the clinical phenotype to the molecular taxonomy and stratified medicine. Allergy 2012; 67: 1475–1482. DOI: 10.1111/all.12049
4. Harris V.R., Cooper A.J. Atopic dermatitis: the new frontier. Med J Aust 2017; 207(8): 351–356. DOI: 10.5694/mja17.00463
5. Matsunaga M.C., Yamauchi P.S. IL-4 and IL-13 Inhibition in Atopic Dermatitis. J Drugs Dermatol 2016; 15(8): 925–929.
6. Kamsteeg M., Bergers M., de Boer, R., Zeeuwen P.L., Hato S.V. et al. Type 2 helper T-cell cytokines induce morphologic and molecular characteristics of atopic dermatitis in human skin equivalent. Am J Pathol 2011; 178: 2091–2099. DOI: 10.1016/j.ajpath.2011.01.037
7. Bao L., Mohan G.C., Alexander J.B., Doo C., Shen K., Bao J., Chan L.S. A molecular mechanism for IL-4 suppression of loricrin transcription in epidermal keratinocytes: implication for atopic dermatitis pathogenesis. Innate Immun 2017; 23(8): 641–647. DOI: 10.1177/1753425917732823
8. Bao L., Shi V.Y., Chan L.S. IL-4 up-regulates epidermal chemotactic, angiogenic, and pro-inflammatory genes and down-regulates antimicrobial genes in vivo and in vitro: relevant in the pathogenesis of atopic dermatitis. Cytokine 2013; 61(2): 419–425. DOI: 10.1016/j.cyto.2012.10.031
9. Shang H., Cao X.L., Wan Y.J., Meng J. Guo L.H. IL-4 Gene Polymorphism May Contribute to an Increased Risk of Atopic Dermatitis in Children. Dis Markers 2016; 2016: 1021942. DOI: 10.1155/2016/1021942
10. Totsuka A., OmoriMiyake M., Kawashima M., Yagi J., Tsunemi Y. Expression of keratin 1, keratin 10, desmoglein 1 and desmocollin 1 in the epidermis: possible downregulation by interleukin-4 and interleukin-13 in atopic dermatitis. Eur J Dermatol 2017; 27(3): 247–253. DOI: 10.1684/ejd.2017.2985
11. Morizane S., Yamasaki K., Kajita A., Ikeda K., Zhan M. et al. TH2 cytokines increase kallikrein 7 expression and function in patients with atopic dermatitis. J Allergy Clin Immunol 2012; 130: 259–261. DOI: 10.1016/j.jaci.2012.03.006
12. Yamasaki K., Gallo R.L. Antimicrobial peptides in human skin disease. Eur J Dermatol 2008; 18: 11–21. DOI: 10.1684/ ejd.2008.0304
13. de BruinWeller M., Thaçi D., Smith C.H., Reich K., Cork M., Radin A. et al. Dupilumab with concomitant topical corticosteroids in adult patients with atopic dermatitis who are not adequately controlled with or are intolerant to ciclosporin A, or when this treatment is medically inadvisable: a placebo-controlled, randomized phase 3 clinical trial (LIBERTY AD CAFÉ). Br J Dermatol 2017; 28. DOI: 10.1111/bjd.16156
14. Gandhi N.A., Pirozzi G., Graham N.M.H. Commonality of the IL-4/IL-13 pathway in atopic diseases. Expert Rev Clin Immunol 2017; 13(5): 425–437. DOI: 10.1080/1744666X.2017.1298443
15. Doran E., Cai F., Holweg C.T.J., Wong K., Brumm J., Arron J.R. Interleukin-13 in Asthma and Other Eosinophilic Disorders. Front Med (Lausanne) 2017; 19(4): 139. DOI: 10.3389/fmed.2017.00139
16. Wang A.X., Xu Landén N. New insights into T cells and their signature cytokines in atopic dermatitis. IUBMB Life 2015; 67(8): 601–610. DOI: 10.1002/iub.1405
17. Wong L.S., Wu T., Lee C.H. Inflammatory and Noninflammatory Itch: Implications in Pathophysiology-Directed Treatments. Int J Mol Sci 2017; 18(7): pii: E1485. DOI: 10.3390/ijms18071485
18. Oh M.H., Oh S.Y., Lu J., Lou H., Myers A.C. et al. TRPA1-dependent pruritus in IL-13-induced chronic atopic dermatitis. J Immunol 2013; 191: 5371–5382. DOI: 10.4049/jimmunol.1300300
19. Oh M.H., Oh S.Y., Yu J., Myers A.C., Leonard W.J. et al. IL-13 induces skin fibrosis in atopic dermatitis by thymic stromal lymphopoietin. J Immunol 2011; 186: 7232–7242. DOI: 10.4049/jimmunol.1100504
20. Popovic B., Breed J., Rees D.G., Gardener M.J., Vinall L.M., Kemp B. et al. Structural Characterisation Reveals Mechanism of IL-13-Neutralising Monoclonal Antibody Tralokinumab as Inhibition of Binding to IL-13Rα1 and IL-13Rα2. J Mol Biol 2017; 429(2): 208–219. DOI: 10.1016/j.jmb.2016.12.005
21. Kim J.E., Kim J.S., Cho D.H., Park H.J. Molecular Mechanisms of Cutaneous Inflammatory Disorder: Atopic Dermatitis. Int J Mol Sci 2016; 17: 1234. DOI:10.3390/ijms17081234
22. Pampura A.N., Svjatkina O.B., Morozova O.V., Dzhal’chinova V.B., Ruzhickaja E.A., Cheburkin A.A., Pogomij N.N. The relationship between interleukin-5 with the characteristics of eosinophils at children with atopic dermatitis. Pediatrija. Zhurnal im. G.N. Speranskogo 2002; 81(5): 8–10. (in Russ)
23. Jeong C., Ahn K., Rho N., Park Y.D., Lee D.Y., Lee J.H. et al. Differential in vivo cytokine mRNA expression in lesional skin of intrinsic vs. extrinsic atopic dermatitis patients using semiquantitative RT-PCR. Clin Exp Allergy 2003; 33: 1717– 1724. DOI: 10.1111/j.1365-2222.2003.01782.x
24. Gürkan A., Yücel A.A., Sönmez C., Keleş Ş., Bostancı İ. Serum Cytokine Profiles in Infants with Atopic Dermatitis. Acta Dermatovenerol Croat 2016; 24(4): 268–273.
25. Vinogradova T.V., Chusljaeva A.A., Varlamov E.E., Ruzhickaja E.A., Suhorukov V.S., Pampura A.N. Recent evaluation of cytokine status of children with atopic dermatitis. Ros vestn perinatol i pediatr 2014; 59(1): 82–87. (in Russ)
26. Nygaard U., Hvid M., Johansen C., Buchner M., Fölster-Holst R., Deleuran M. Vestergaard C4. TSLP, IL-31, IL-33 and sST2 are new biomarkers in endophenotypic profiling of adult and childhood atopic dermatitis. J Eur Acad Dermatol Venereol 2016; 30(11): 1930–1938. DOI: 10.1111/jdv.13679
27. Szegedi K., Kremer A.E., Kezic S., Teunissen M.B., Bos J.D. et al. Increased frequencies of IL-31-producing T cells are found in chronic atopic dermatitis skin. Exp Dermatol 2012; 21: 431–436. DOI: 10.1111/j.1600-0625.2012.01487.x
28. Cornelissen C., Marquardt Y., Czaja K., Wenzel J., Frank J. et al. IL-31 regulates differentiation and filaggrin expression in human organotypic skin models. J Allergy Clin Immunol 2012; 129: 426–433. DOI: 10.1016/j.jaci.2011.10.042
29. Marsella R., Ahrens K., Sanford R. Investigation of the correlation of serum IL-31 with severity of dermatitis in an experimental model of canine atopic dermatitis using beagle dogs. Vet Dermatol 2017; 28: 441–442. DOI: 10.1111/vde.12500
30. Furue M., Yamamura K., Kido-Nakahara M., Nakahara T, Fukui Y. Emerging role of interleukin-31 and interleukin-31 receptor in pruritus in atopic dermatitis. Allergy 2017. DOI: 10.1111/all.13239
31. Kasraie S., Niebuhr M., Werfel T. Interleukin (IL)231 activates signal transducer and activator of transcription (STAT)21, STAT-5 and extracellular signal-regulated kinase 1/2 and down-regulates IL-12p40 production in activated human macrophages. Allergy 2013; 68: 739–747. DOI: 10.1111/ all.12152
32. Nakayamada S., Kanno Y., Takahashi H., Jankovic D., Lu K.T. et al. Early Th1 cell differentiation is marked by a Tfh cell-like transition. Immunity 2011; 35: 919–931. DOI: 10.1016/j.immuni.2011.11.012
33. Sawada E., Yoshida N., Sugiura A., Imokawa G. Th1 cytokines accentuate but Th2 cytokines attenuate ceramide production in the stratum corneum of human epidermal equivalents: an implication for the disrupted barrier mechanism in atopic dermatitis. J Dermatol 2012; 68: 25–35. DOI: 10.1016/j. jdermsci.2012.07.004
34. Brar K., Leung D.Y. Recent considerations in the use of recombinant interferon gamma for biological therapy of atopic dermatitis. Expert Opin Biol Ther 2016; 16(4): 507–514. DOI: 10.1517/14712598.2016.1135898
35. Johnson-Huang L.M., Suarez-Farinas M., Pierson K.C., Fuentes-Duculan J., Cueto I. et al. A single intradermal injection of IFN-gamma induces an inflammatory state in both non-lesional psoriatic and healthy skin. J Invest Dermatol 2012; 132: 1177–1187. DOI: 10.1038/jid.2011.458
36. Di Bari F. Atopic dermatitis and alpha-chemokines. Clin Ter 2015; 166(3): 182-187. DOI: 10.7417/T.2015.1852. DOI: 10.7417/T.2015.1852
37. Nograles K.E., Zaba L.C., Shemer A., Fuentes-Duculan J., Cardinale I. et al. IL-22-producing T22 T cells account for upregulated IL-22 in atopic dermatitis despite reduced IL-17-producing TH17 T cells. J Allergy Clin Immunol 2009; 123: 1244–1252. DOI: 10.1016/j.jaci.2009.03.041
38. Glocova I., Brück J., Geisel J., Müller-Hermelink E., Widmaier K., Yazdi A.S. et al. Induction of skin-pathogenic Th22 cells by epicutaneous allergen exposure. J Dermatol Sci 2017; 87(3): 268–277. DOI: 10.1016/j.jdermsci.2017.06.006
39. Souwer Y., Szegedi K., Kapsenberg M. et al. IL-17 and IL-22 in atopic allergic disease. Curr Opin Immunol 2010; 22: 821– 826. DOI: 10.1016/j.coi.2010.10.013
40. Hayashida S., Uchi H., Takeuchi S., Esaki H., Moroi Y. et al. Significant correlation of serum IL-22 levels with CCL17 levels in atopic dermatitis. J Dermatol Sci 2011; 61: 78–79. DOI: 10.1016/j.jdermsci.2010.08.013
41. Lou H., Lu J., Choi E.B., Oh M.H., Jeong M., Barmettler S., Zhu Z., Zheng T. Expression of IL-22 in the Skin Causes Th2-Biased Immunity, Epidermal Barrier Dysfunction, and Pruritus via Stimulating Epithelial Th2 Cytokines and the GRP Pathway. J Immunol 2017; 198(7): 2543–2555. DOI: 10.4049/jimmunol.1600126
42. Czarnowicki T., Gonzalez J., Shemer A., Malajian D., Xu H., Zheng X. et al. Severe atopic dermatitis is characterized by selective expansion of circulating TH2/TC2 and TH22/TC22, but not TH17/TC17, cells within the skin-homing T-cell population. J Allergy Clin Immunol 2015; 136(1): 104–115. e7. DOI: 10.1016/j.jaci.2015.01.020
43. Sabat R., Ouyang W., Wolk K. Therapeutic opportunities of the IL-22-IL-22R1 system. Nat Rev Drug Discov 2014; 13: 21–38. DOI: 10.1038/nrd4176
44. Malhotra N., Yoon J., Leyva-Castillo J.M., Galand C., Archer N., Miller L.S., Geha R.S. IL-22 derived from γδ T cells restricts Staphylococcus aureus infection of mechanically injured skin. J Allergy Clin Immunol 2016; 138(4): 1098– 1107.e DOI: 10.1016/j.jaci.2016.07.001
45. Varlamov E.E., Elisjutina O.G., Vinogradova T.V., Fedenko E.S., Pampura A.N. Pathogenesis specificity of cytokine profile in atopic dermatitis patients depending on the age. Ros allergol zhurn 2016; 4–5: 37–42. (in Russ)
46. Miyagaki Т., Sugaya М., Suga H. Kamata M., Ohmatsu H., Fujita H. et al. IL-22, but Not IL-17, Dominant Environment in Cutaneous T-cell Lymphoma. Clin Cancer Res 2011; 17: 7529–7538. DOI:10.1158/1078-0432.CCR-11-1192 Zhou F., Lauretti E., di Meco A., Ciric B., Gonnella P. et al. Intravenous transfer of apoptotic cell-treated dendritic cells leads to immune tolerance by blocking Th17 cell activity. Immuno-biol 2013; 218: 1069–1076.
47. Qu N., Xu M., Mizoguchi I., Furusawa J., Kaneko K., Watanabe K. et al. Pivotal roles of T-helper 17-related cytokines, IL-17, IL-22, and IL-23, in inflammatory diseases. Clin Dev Immunol 2013; 2013: 968549. DOI: 10.1155/2013/968549
48. Tan Q., Yang H., Liu E.M., Wang H. Establishing a Role for Interleukin-17 in Atopic Dermatitis-Related Skin Inflammation. J Cutan Med Surg 2017; 21(4): 308–315. DOI: 10.1177/1203475417697651
49. Floudas A., Saunders S.P., Moran T., Schwartz C., Hams E., FitzgeraldD.C. et al. IL-17 Receptor A Maintains and Protects the Skin Barrier To Prevent Allergic Skin Inflammation. J Immunol 2017; 199(2): 707–717. DOI: 10.4049/ jimmunol.1602185
50. Gutowska-Owsiak D., Schaupp A.L., Salimi M., Selvaku-mar T.A., McPherson T. et al. IL-17 downregulates filaggrin and affects keratinocyte expression of genes associated with cellular adhesion. Exp. Dermatol 2012; 21: 104–110. DOI: 10.4049/jimmunol.1602185
51. Yuki T., Tobiishi M., Kusaka-Kikushima A., Ota Y., Tokura Y. Impaired Tight Junctions in Atopic Dermatitis Skin and in a Skin-Equivalent Model Treated with Interleukin-17. PLoS One 2016; 11(9): e0161759. DOI: 10.1371/journal. pone.0161759
52. Nakajima S., Kitoh A., Egawa G., Natsuaki Y., Nakamizo S. et al. IL-17A as an inducer for Th2 immune responses in mu-rine atopic dermatitis models. J Invest Dermatol 2014; 134: 2122–2130. DOI: 10.1371/journal.pone.0161759
53. Bogiatzi S.I., Guillot-Delost M., Cappuccio A., Bichet J.C., Chouchane-Mlik O. et al. Multiple-checkpoint inhibition of thymic stromal lymphopoietin-induced TH2 response by TH17-related cytokines. J Allergy Clin Immunol 2012; 130: 233–240. DOI: 10.1038/jid.2014.51
54. Han S.C., Kang G.J., Ko Y.J., Kang H.K., Moon S.W. et al. Fermented fish oil suppresses T helper 1/2 cell response in a mouse model of atopic dermatitis via generation of CD41CD251Foxp31T cells. BMC Immunol 2012; 13: 44. DOI: 10.1016/j.jaci.2012.04.038
55. Schlapbach C., Gehad A., Yang C., Watanabe R., Guenova E. et al. Human TH9 cells are skin-tropic and have autocrine and paracrine proinflammatory capacity. Sci Transl Med 2014; 6: 219ra218. DOI: 10.1186/1471-2172-13-44
56. Hamza A.M., Omar S.S., Abo El-Wafa R.A., Elatrash M.J. Expression levels of transcription factor PU.1 and interleukin-9 in atopic dermatitis and their relation to disease severity and eruption types. Int J Dermatol 2017; 56(5): 534–539. DOI: 10.1111/ijd.13579
57. Ma L., Xue H.B., Guan X.H., Shu C.M., Zhang J.H., Yu J. Possible pathogenic role of T helper type 9 cells and interleukin (IL)-9 in atopic dermatitis. Clin Exp Immunol 2014; 175(1): 25–31. DOI: 10.1111/cei.12198
58. Namkung J.H., Lee J.E., Kim E., Park G.T., Yang H.S. et al. An association between IL-9 and IL-9 receptor gene polymorphisms and atopic dermatitis in a Korean population. J Dermatol Sci 2011; 62: 16–21. DOI: 10.1111/cei.12198
59. Li A.G., Wang D., Feng X.H., Wang X.J. Latent TGFbeta1 overexpression in keratinocytes results in a severe psoriasis-like skin disorder. EMBO J 2004; 23: 1770–1781. DOI: 10.1016/j.jdermsci.2011.01.007
60. Varlamov E.E., Vinogradova T.V., Chusljaeva A.A., Pampura A.N. Features of the cytokine profile in infants with multiple food protein intolerance. Ros Allergol zhurn 2012; 5: 76–80. (in Russ)
61. Snast I., Reiter O., Hodak. E., Friedland R., Mimouni D., Leshem Y.A. Are Biologics Efficacious in Atopic Dermatitis? A Systematic Review and Meta-Analysis. Am J Clin Dermatol 2017; 2. DOI: 10.1007/s40257-017-0324-7
Review
For citations:
Varlamov E.E., Pampura A.N., Sukhorukov V.S. The importance of cytokines for the atopic dermatitis pathogenesis. Rossiyskiy Vestnik Perinatologii i Pediatrii (Russian Bulletin of Perinatology and Pediatrics). 2018;63(1):28-33. (In Russ.) https://doi.org/10.21508/1027-4065-2018-63-1-28-33
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