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Cited by 128Dermatology and Skin DiseasesContact Dermatitis and AllergiesAsthma and respiratory diseases

Multiple roles for cytokines in atopic dermatitis: from pathogenic mediators to endotype-specific biomarkers to therapeutic targets

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Fania, Luca, Moretta, Gaia, Antonelli, Flaminia, Scala, Enrico, Abeni, Damiano, Albanesi, Cristina, Madonna, Stefania·2022·International Journal of Molecular Sciences
DOI 10.3390/ijms23052684PMC PMC8910412
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Abstract

Atopic dermatitis (AD) is one of the most common chronic inflammatory skin diseases, which generally presents with intense itching and recurrent eczematous lesions. AD affects up to 20% of children and 10% of adults in high-income countries. The prevalence and incidence of AD have increased in recent years. The onset of AD mostly occurs in childhood, although in some cases AD may persist in adult life or even manifest in middle age (adult-onset AD). AD pathophysiology is made of a complex net, in which genetic background, skin barrier dysfunction, innate and adaptive immune responses, as well as itch contribute to disease development, progression, and chronicization. One of the most important features of AD is skin dehydration, which is mainly caused by filaggrin mutations that determine trans-epidermal water loss, pH alterations, and antigen penetration. In accordance with the "outside-inside" theory of AD pathogenesis, in a context of an altered epidermal barrier, antigens encounter epidermal antigen presentation cells (APCs), such as epidermal Langerhans cells and inflammatory epidermal dendritic cells, leading to their maturation and Th-2 cell-mediated inflammation. APCs also bear trimeric high-affinity receptors for immunoglobulin E (IgE), which induce IgE-mediated sensitizations as part of pathogenic mechanisms leading to AD. In this review, we discuss the role of cytokines in the pathogenesis of AD, considering patients with various clinical AD phenotypes. Moreover, we describe the cytokine patterns in patients with AD at different phases of the disease evolution, as well as in relation to different phenotypes/endotypes, including age, race, and intrinsic/extrinsic subtypes. We also discuss the outcomes of current biologics for AD, which corroborate the presence of multiple cytokine axes involved in the background of AD. A deep insight into the correlation between cytokine patterns and the related clinical forms of AD is a crucial step towards increasingly personalized, and therefore more efficient therapy.

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  • In acute eczema, the lesions are supported by tissue expression of IL-1alpha and IL-1beta, IL-33, IL-4, IL-13, and IL-22.

    “In acute eczema, the lesions are supported by tissue expression of IL-1alpha and IL-1beta, IL-33, IL-4, IL-13, and IL-22.”

    From Update on the pathogenesis of atopic dermatitis. (2024) · cites this paper as [82]

    Section 2.1 (Role of Cytokines in Acute AD; page unavailable) links IL-4, IL-13, and IL-22 to acute lesions and reports abundant IL-33 in lesional epidermis. It describes IL-1α release after injury and elevated IL-1β in patients with FLG mutations, but does not establish elevated tissue expression of both across acute lesions. It also says whether IL-33 causes AD or results from it is unclear, so the claim that its expression supports lesions is stronger than the source warrants. (LLM, conf=0.84)

    Experimental — accuracy not yet measured

  • In subacute eczema, the main cytokines are IL-4, IL-13, IL-25, IL-31, IL-33 and TLSP.

    “In subacute eczema, the main cytokines are IL-4, IL-13, IL-25, IL-31, IL-33 and TLSP.”

    From Update on the pathogenesis of atopic dermatitis. (2024) · cites this paper as [82]

    Section 2.1 (page not provided) discusses IL-4, IL-13, IL-25, IL-33 and TSLP in acute atopic dermatitis; Section 2.2 discusses IL-31 in chronic atopic dermatitis. The paper does not identify this list as the main cytokines of subacute eczema. The claim also appears to transpose TSLP as “TLSP.” (LLM, conf=0.88)

    Experimental — accuracy not yet measured

  • In chronic eczema, there is a predominance of Th1 and Th17 cytokines: IFNγ, TNFα, IL-17A, IL-17F.

    “In chronic eczema, there is a predominance of Th1 and Th17 cytokines: IFNγ, TNFα, IL-17A, IL-17F.82”

    From Update on the pathogenesis of atopic dermatitis. (2024) · cites this paper as [82]

    Section 2.2 (page not specified) links chronic atopic dermatitis to intensified Th1 and Th17 responses, accumulation of IL-17A and IL-17F, and activity of IFN-γ and TNF-α. It does not say Th1 and Th17 predominate: it says Th2 responses also intensify during progression to chronic disease. (LLM, conf=0.88)

    Experimental — accuracy not yet measured

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  1. [2]Barbarot S. Auziere S. Gadkari A. Girolomoni G. Puig L. Simpson E.L. Margolis D.J. de Bruin-Weller M. Eckert L. Epidemiology of atopic dermatitis in adults: Results from an international survey Allergy 2018 73 1284 1293 10.1111/all.13401 29319189 · DOI
  2. [3]Laughter M.R. Maymone M.B.C. Mashayekhi S. Arents B.W.M. Karimkhani C. Langan S.M. Dellavalle R.P. Flohr C. The global burden of atopic dermatitis: Lessons from the Global Burden of Disease Study 1990–2017 Br. J. Dermatol. 2021 184 304 309 10.1111/bjd.19580 33006135 · DOI
  3. [4]Langan S.M. Irvine A.D. Weidinger S. Atopic dermatitis Lancet 2020 396 345 360 10.1016/S0140-6736(20)31286-1 32738956 · DOI
  4. [5]Kim J. Kim B.E. Leung D.Y.M. Pathophysiology of atopic dermatitis: Clinical implications Allergy Asthma Proc. 2019 40 84 92 10.2500/aap.2019.40.4202 30819278 PMC6399565 · DOI
  5. [7]Girolomoni G. Abeni D. Masini C. Sera F. Ayala F. Belloni-Fortina A. Bonifazi E. Fabbri P. Gelmetti C. Monfrecola G. The epidemiology of atopic dermatitis in Italian schoolchildren Allergy 2003 58 420 425 10.1034/j.1398-9995.2003.00112.x 12752329 · DOI
  6. [9]Eyerich S. Onken A.T. Weidinger S. Franke A. Nasorri F. Pennino D. Grosber M. Pfab F. Schmidt-Weber C.B. Mempel M. Mutual antagonism of T cells causing psoriasis and atopic eczema N. Engl. J. Med. 2011 365 231 238 10.1056/NEJMoa1104200 21774711 · DOI
  7. [12]Chieosilapatham P. Kiatsurayanon C. Umehara Y. Trujillo-Paez J.V. Peng G. Yue H. Nguyen L.T.H. Niyonsaba F. Keratinocytes: Innate immune cells in atopic dermatitis Clin. Exp. Immunol. 2021 204 296 309 10.1111/cei.13575 33460469 PMC8119845 · DOI · Paper page
  8. [14]Palmer C.N. Irvine A.D. Terron-Kwiatkowski A. Zhao Y. Liao H. Lee S.P. Goudie D.R. Sandilands A. Campbell L.E. Smith F.J. Common loss-of-function variants of the epidermal barrier protein filaggrin are a major predisposing factor for atopic dermatitis Nat. Genet. 2006 38 441 446 10.1038/ng1767 16550169 · DOI · Paper page
  9. [15]Hönzke S. Wallmeyer L. Ostrowski A. Radbruch M. Mundhenk L. Schäfer-Korting M. Hedtrich S. Influence of Th2 Cytokines on the Cornified Envelope, Tight Junction Proteins, and ß-Defensins in Filaggrin-Deficient Skin Equivalents J. Investig. Dermatol. 2016 136 631 639 10.1016/j.jid.2015.11.007 27015451 · DOI
  10. [16]Kezic S. O’Regan G.M. Lutter R. Jakasa I. Koster E.S. Saunders S. Caspers P. Kemperman P.M. Puppels G.J. Sandilands A. Filaggrin loss-of-function mutations are associated with enhanced expression of IL-1 cytokines in the stratum corneum of patients with atopic dermatitis and in a murine model of filaggrin deficiency J. Allergy Clin. Immunol. 2012 129 1031 1039.e1 10.1016/j.jaci.2011.12.989 22322004 PMC3627959 · DOI
  11. [17]Archer N.K. Jo J.H. Lee S.K. Kim D. Smith B. Ortines R.V. Wang Y. Marchitto M.C. Ravipati A. Cai S.S. Injury, dysbiosis, and filaggrin deficiency drive skin inflammation through keratinocyte IL-1α release J. Allergy Clin. Immunol. 2019 143 1426 1443.e6 10.1016/j.jaci.2018.08.042 30240702 PMC6424655 · DOI · Paper page
  12. [18]Savinko T. Matikainen S. Saarialho-Kere U. Lehto M. Wang G. Lehtimäki S. Karisola P. Reunala T. Wolff H. Lauerma A. IL-33 and ST2 in atopic dermatitis: Expression profiles and modulation by triggering factors J. Investig. Dermatol. 2012 132 1392 1400 10.1038/jid.2011.446 22277940 · DOI
  13. [19]Imai Y. Interleukin-33 in atopic dermatitis J. Dermatol. Sci. 2019 96 2 7 10.1016/j.jdermsci.2019.08.006 31455506 · DOI
  14. [20]Imai Y. Yasuda K. Sakaguchi Y. Haneda T. Mizutani H. Yoshimoto T. Nakanishi K. Yamanishi K. Skin-specific expression of IL-33 activates group 2 innate lymphoid cells and elicits atopic dermatitis-like inflammation in mice Proc. Natl. Acad. Sci. USA 2013 110 13921 13926 10.1073/pnas.1307321110 23918359 PMC3752227 · DOI
  15. [21]Roan F. Obata-Ninomiya K. Ziegler S.F. Epithelial cell-derived cytokines: More than just signaling the alarm J. Clin. Investig. 2019 129 1441 1451 10.1172/JCI124606 30932910 PMC6436879 · DOI
  16. [22]Garcovich S. Maurelli M. Gisondi P. Peris K. Yosipovitch G. Girolomoni G. Pruritus as a Distinctive Feature of Type 2 Inflammation Vaccines 2021 9 303 10.3390/vaccines9030303 33807098 PMC8005108 · DOI
  17. [23]Ryu W.I. Lee H. Bae H.C. Ryu H.J. Son S.W. IL-33 down-regulates filaggrin expression by inducing STAT3 and ERK phosphorylation in human keratinocytes J. Dermatol. Sci. 2016 82 131 134 10.1016/j.jdermsci.2016.01.011 26867960 · DOI
  18. [24]Topal F.A. Zuberbier T. Makris M.P. Hofmann M. The role of IL-17, IL-23 and IL-31, IL-33 in allergic skin diseases Curr. Opin. Allergy Clin. Immunol. 2020 20 367 373 10.1097/ACI.0000000000000658 32590505 · DOI
  19. [25]Chieosilapatham P. Ikeda S. Ogawa H. Niyonsaba F. Tissue-specific Regulation of Innate Immune Responses by Human Cathelicidin LL-37 Curr. Pharm. Des. 2018 24 1079 1091 10.2174/1381612824666180327113418 29589544 · DOI
  20. [26]Coates M. Blanchard S. MacLeod A.S. Innate antimicrobial immunity in the skin: A protective barrier against bacteria, viruses, and fungi PLoS Pathog. 2018 14 e1007353 10.1371/journal.ppat.1007353 30522130 PMC6283644 · DOI
  21. [27]Miller L.S. Toll-like receptors in skin Adv. Dermatol. 2008 24 71 87 10.1016/j.yadr.2008.09.004 19256306 PMC2633625 · DOI
  22. [28]Di Cesare A. Di Meglio P. Nestle F.O. A role for Th17 cells in the immunopathogenesis of atopic dermatitis? J. Investig. Dermatol. 2008 128 2569 2571 10.1038/jid.2008.283 18927538 · DOI
  23. [30]Wang Y.H. Liu Y.J. Thymic stromal lymphopoietin, OX40-ligand, and interleukin-25 in allergic responses Clin. Exp. Allergy 2009 39 798 806 10.1111/j.1365-2222.2009.03241.x 19400908 PMC2744577 · DOI
  24. [31]Lee K.H. Cho K. Kim J.Y. Kim J.Y. Baek J.H. Woo S.Y. Kim J.W. Filaggrin knockdown and Toll-like receptor 3 (TLR3) stimulation enhanced the production of thymic stromal lymphopoietin (TSLP) from epidermal layers Exp. Dermatol. 2011 20 149 151 10.1111/j.1600-0625.2010.01203.x 21255094 · DOI
  25. [32]Cianferoni A. Spergel J. The importance of TSLP in allergic disease and its role as a potential therapeutic target Expert Rev. Clin. Immunol. 2014 10 1463 1474 10.1586/1744666X.2014.967684 25340427 PMC4332833 · DOI
  26. [33]Xie Y. Takai T. Chen X. Okumura K. Ogawa H. Long TSLP transcript expression and release of TSLP induced by TLR ligands and cytokines in human keratinocytes J. Dermatol. Sci. 2012 66 233 237 10.1016/j.jdermsci.2012.03.007 22520928 · DOI
  27. [34]Chieosilapatham P. Ogawa H. Niyonsaba F. Current insights into the role of human β-defensins in atopic dermatitis Clin. Exp. Immunol. 2017 190 155 166 10.1111/cei.13013 28708318 PMC5629447 · DOI
  28. [35]Wilson S.R. Thé L. Batia L.M. Beattie K. Katibah G.E. McClain S.P. Pellegrino M. Estandian D.M. Bautista D.M. The epithelial cell-derived atopic dermatitis cytokine TSLP activates neurons to induce itch Cell 2013 155 285 295 10.1016/j.cell.2013.08.057 24094650 PMC4041105 · DOI
  29. [36]Borowczyk J. Shutova M. Brembilla N.C. Boehncke W.H. IL-25 (IL-17E) in epithelial immunology and pathophysiology J. Allergy Clin. Immunol. 2021 148 140 152 10.1016/j.jaci.2020.12.628 33485651 · DOI
  30. [37]Liu Y. Shao Z. Shangguan G. Bie Q. Zhang B. Biological Properties and the Role of IL-25 in Disease Pathogenesis J. Immunol. Res. 2018 23 6519465 10.1155/2018/6519465 PMC6174801 30345318 · DOI
  31. [38]Hvid M. Vestergaard C. Kemp K. Christensen G.B. Deleuran B. Deleuran M. IL-25 in atopic dermatitis: A possible link between inflammation and skin barrier dysfunction? J. Investig. Dermatol. 2011 131 150 157 10.1038/jid.2010.277 20861853 · DOI
  32. [39]Dubin C. Del Duca E. Guttman-Yassky E. The IL-4, IL-13 and IL-31 pathways in atopic dermatitis Expert Rev. Clin. Immunol. 2021 17 835 852 10.1080/1744666X.2021.1940962 34106037 · DOI
  33. [40]Oetjen L.K. Mack M.R. Feng J. Whelan T.M. Niu H. Guo C.J. Chen S. Trier A.M. Xu A.Z. Tripathi S.V. Sensory Neurons Co-opt Classical Immune Signaling Pathways to Mediate Chronic Itch Cell 2017 171 217 228.e13 10.1016/j.cell.2017.08.006 28890086 PMC5658016 · DOI · Paper page
  34. [41]Namita A. Gandhi A. Bennett B.L. Graham N.M.H. Pirozzi G. Stahl N. Yancopoulos G.D. Targeting key proximal drivers of type 2 inflammation in disease Nat. Rev. Drug Discov. 2016 15 35 50 10.1038/nrd4624 26471366 · DOI · Paper page
  35. [42]Calderón M.A. Devalia J.L. Prior A.J. Sapsford R.J. Davies R.J. A comparison of cytokine release from epithelial cells cultured from nasal biopsy specimens of atopic patients with and without rhinitis and nonatopic subjects without rhinitis J. Allergy Clin. Immunol. 1997 99 65 76 10.1016/S0091-6749(97)70302-6 9003213 · DOI
  36. [44]Jin M. Yoon J. From Bench to Clinic: The Potential of Therapeutic Targeting of the IL-22 Signaling Pathway in Atopic Dermatitis Immune Netw. 2018 18 e42 10.4110/in.2018.18.e42 30619628 PMC6312894 · DOI
  37. [45]Yoon J. Leyva-Castillo J.M. Wang G. Galand C. Oyoshi M.K. Kumar L. Hoff S. He R. Chervonsky A. Oppenheim J.J. IL-23 induced in keratinocytes by endogenous TLR4 ligands polarizes dendritic cells to drive IL-22 responses to skin immunization J. Exp. Med. 2016 213 2147 2166 10.1084/jem.20150376 27551155 PMC5032726 · DOI
  38. [46]Gittler J.K. Shemer A. Suárez-Fariñas M. Fuentes-Duculan J. Gulewicz K.J. Wang C.Q.F. Mitsui H. Cardinale I. de Guzman Strong C. Krueger J.G. Progressive activation of T(H)2/T(H)22 cytokines and selective epidermal proteins characterizes acute and chronic atopic dermatitis J. Allergy Clin. Immunol. 2012 130 1344 1354 10.1016/j.jaci.2012.07.012 22951056 PMC3991245 · DOI · Paper page
  39. [47]Tsoi L.C. Rodriguez E. Stölzl D. Wehkamp U. Sun J. Gerdes S. Sarkar M.K. Hübenthal M. Zeng C. Uppala R. Progression of acute-to-chronic atopic dermatitis is associated with quantitative rather than qualitative changes in cytokine responses J. Allergy Clin. Immunol. 2020 145 1406 1415 10.1016/j.jaci.2019.11.047 31891686 PMC7214216 · DOI
  40. [48]Albanesi A. Scarponi C. Sebastiani S. Cavani A. Federici M. De Pità O. Puddu P. Girolomoni G. IL-4 enhances keratinocyte expression of CXCR3 agonistic chemokines J. Immunol. 2000 165 1395 1402 10.4049/jimmunol.165.3.1395 10903743 · DOI
  41. [49]Mercurio L. Failla C.M. Capriotti L. Scarponi C. Facchiano F. Morelli M. Rossi S. Pagnanelli G. Albanesi C. Cavani A. Interleukin (IL)-17/IL-36 axis participates to the crosstalk between endothelial cells and keratinocytes during inflammatory skin responses PLoS ONE 2020 15 e0222969 10.1371/journal.pone.0222969 32352958 PMC7192413 · DOI
  42. [50]Mercurio L. Morelli M. Scarponi C. Eisenmesser E.Z. Doti N. Pagnanelli G. Gubinelli E. Mazzanti C. Cavani A. Ruvo M. IL-38 has an anti-inflammatory action in psoriasis and its expression correlates with disease severity and therapeutic response to anti-IL-17A treatment Cell Death Dis. 2018 9 1104 10.1038/s41419-018-1143-3 30377293 PMC6207563 · DOI
  43. [51]Madonna S. Girolomoni G. Dinarello C.A. Albanesi C. The Significance of IL-36 Hyperactivation and IL-36R Targeting in Psoriasis Int. J. Mol. Sci. 2019 20 3318 10.3390/ijms20133318 31284527 PMC6650959 · DOI
  44. [52]Foster A.M. Baliwag J. Chen C.S. Guzman A.M. Stoll S.W. Gudjonsson J.E. Ward N.L. Johnston A. IL-36 promotes myeloid cell infiltration, activation, and inflammatory activity in skin J. Immunol. 2014 192 6053 6061 10.4049/jimmunol.1301481 24829417 PMC4048788 · DOI
  45. [53]Shao S. Tsoi L.C. Swindell W.R. Chen J. Uppala R. Billi A.C. Xing X. Zeng C. Sarkar M.K. Wasikowski R. IRAK2 Has a Critical Role in Promoting Feed-Forward Amplification of Epidermal Inflammatory Responses J. Investig. Dermatol. 2021 141 2436 2448 10.1016/j.jid.2021.03.019 33864770 PMC9423738 · DOI
  46. [54]Eyerich S. Metz M. Bossios A. Eyerich K. New biological treatments for asthma and skin allergies Allergy 2020 75 546 560 10.1111/all.14027 31444793 · DOI
  47. [56]Datsi A. Steinhoff M. Ahmad F. Alam M. Buddenkotte J. New and emerging treatments for inflammatory itch Allergy 2021 76 2982 2997 10.1111/all.14791 33629401 · DOI
  48. [57]Sonkoly E. Muller A. Lauerma A.I. Pivarcsi A. Soto H. Kemeny L. Alenius H. Dieu-Nosjean M.C. Meller S. Rieker J. IL-31: A new link between T cells and pruritus in atopic skin inflammation J. Allergy Clin. Immunol. 2006 117 411 417 10.1016/j.jaci.2005.10.033 16461142 · DOI
  49. [58]Nobbe S. Dziunycz P. Mühleisen B. Bilsborough J. Dillon S.R. French L.E. Hofbauer F.F.L. IL-31 expression by inflammatory cells is preferentially elevated in atopic dermatitis Acta Derm.-Venereol. 2012 92 24 28 10.2340/00015555-1191 22041865 · DOI
  50. [59]Szegedi K. Kremer A.E. Kezic S. Teunissen M.B.M. Bos J.D. Luiten R.M. Res P.C. Middelkamp-Hup M.S. Increased frequencies of IL-31-producing T cells are found in chronic atopic dermatitis skin Exp. Dermatol. 2012 21 431 436 10.1111/j.1600-0625.2012.01487.x 22621183 · DOI
  51. [60]Ezzat M.H.M. Hasan Z.E. Shaheen K.Y.A. Serum measurement of interleukin-31 (IL-31) in paediatric atopic dermatitis: Elevated levels correlate with severity scoring J. Eur. Acad. Dermatol. Venereol. 2011 25 334 339 10.1111/j.1468-3083.2010.03794.x 21294778 · DOI
  52. [61]Raap U. Weißmantel S. Gehring M. Eisenberg A.M. Kapp A. Fölster-Holst R. IL-31 significantly correlates with disease activity and Th2 cytokine levels in children with atopic dermatitiS Pediatr. Allergy Immunol. 2012 23 285 288 10.1111/j.1399-3038.2011.01241.x 22509760 · DOI
  53. [62]Kato A. Fujii E. Watanabe T. Takashima Y. Matsushita H. Furuhashi T. Morita A. Distribution of IL-31 and its receptor expressing cells in skin of atopic dermatitis J. Dermatol. Sci. 2014 74 229 235 10.1016/j.jdermsci.2014.02.009 24667097 · DOI
  54. [63]Cornelissen C. Marquardt Y. Czaja K. Wenzel J. Frank J. Lüscher-Firzlaff J. Lüscher B. Baron J.M. IL-31 regulates differentiation and filaggrin expression in human organotypic skin models J. Allergy Clin. Immunol. 2012 129 426 433.e8 10.1016/j.jaci.2011.10.042 22177328 · DOI
  55. [64]Yosipovitch G. Berger T. Fassett M.S. Neuroimmune interactions in chronic itch of atopic dermatitis J. Eur. Acad. Dermatol. Venereol. 2020 34 239 250 10.1111/jdv.15973 31566796 PMC7027518 · DOI
  56. [65]Fujii M. Current Understanding of Pathophysiological Mechanisms of Atopic Dermatitis: Interactions among Skin Barrier Dysfunction, Immune Abnormalities and Pruritus Biol. Pharm. Bull. 2020 43 12 19 10.1248/bpb.b19-00088 31902917 · DOI
  57. [66]Czarnowicki T. He H. Krueger J.G. Guttman-Yassky E. Atopic dermatitis endotypes and implications for targeted therapeutics J. Allergy Clin. Immunol. 2019 143 1 11 10.1016/j.jaci.2018.10.032 30612663 · DOI
  58. [67]Brunner P.M. Israel A. Zhang N. Leonard A. Wen U.C. Huynh T. Tran G. Lyon S. Rodriguez G. Immaneni S. Early-onset pediatric atopic dermatitis is characterized by TH 2/TH 17/TH 22-centered inflammation and lipid alterations J. Allergy Clin. Immunol. 2018 141 2094 2106 10.1016/j.jaci.2018.02.040 29731129 · DOI
  59. [68]Nomura T. Wu J. Kabashima K. Guttman-Yassky E. Endophenotypic Variations of Atopic Dermatitis by Age, Race, and Ethnicity J. Allergy Clin. Immunol. Pract. 2020 8 1840 1852 10.1016/j.jaip.2020.02.022 32499033 · DOI
  60. [69]Trichot C. Faucheux L. Karpf L. Grandclaudon M. Pattarini L. Bagot M. Mahévas T. Jachiet M. Saussine A. Bouaziz J.D. Th cell diversity and response to dupilumab in patients with atopic dermatitis J. Allergy Clin. Immunol. 2021 147 756 759 10.1016/j.jaci.2020.05.037 32526313 · DOI
  61. [70]Renert-Yuval Y. Thyssen J.P. Bissonnette R. Bieber T. Kabashima K. Hijnen D. Guttman-Yassky E. Biomarkers in atopic dermatitis—A review on behalf of the International Eczema Council J. Allergy Clin. Immunol. 2021 147 1174 1190.e1 10.1016/j.jaci.2021.01.013 33516871 PMC11304440 · DOI · Paper page
  62. [71]Esaki H. Brunner P.M. Renert-Yuval Y. Czarnowicki T. Huynh T. Tran G. Lyon S. Rodriguez G. Immaneni S. Johnson D.B. Early-onset pediatric atopic dermatitis is TH2 but also TH17 polarized in skin J. Allergy Clin. Immunol. 2016 138 1639 1651 10.1016/j.jaci.2016.07.013 27671162 · DOI · Paper page
  63. [73]Pavel A.B. Renert-Yuval J. Wu J. Del Duca E. Diaz A. Lefferdink R. Fang M.M. Canter T. Rangel S.M. Zhang N. Tape strips from early-onset pediatric atopic dermatitis highlight disease abnormalities in nonlesional skin Allergy 2021 76 314 325 10.1111/all.14490 32639640 PMC9285647 · DOI
  64. [74]Thijs J.L. Strickland I. Bruijnzeel-Koomen C.A.F.M. Nierkens S. Giovannone B. Csomor E. Sellman B.R. Mustelin T. Sleeman M.A. de Bruin-Weller M.S. Moving toward endotypes in atopic dermatitis: Identification of patient clusters based on serum biomarker analysis J. Allergy Clin. Immunol. 2017 140 730 737 10.1016/j.jaci.2017.03.023 28412391 · DOI
  65. [75]Bakker D.S. Nierkens S. Knol E.F. Giovannone B. Delemarre E.M. van der Schaft J. van Wijk F. de Bruin-Weller M.S. Drylewicz J. Thijs J.L. Confirmation of multiple endotypes in atopic dermatitis based on serum biomarkers J. Allergy Clin. Immunol. 2021 147 189 198 10.1016/j.jaci.2020.04.062 32526312 · DOI
  66. [76]Lauffer F. Baghin V. Standl M. Stark S.P. Jargosch M. Wehrle J. Thomas J. Schmidt-Weber C.B. Biedermann T. Eyerich S. Predicting persistence of atopic dermatitis in children using clinical attributes and serum proteins Allergy 2021 76 1158 1172 10.1111/all.14557 32794228 · DOI
  67. [78]Czarnowicki T. Esaki H. Gonzalez J. Malajian D. Shemer A. Noda S. Talasila S. Berry A. Gray J. Becker L. Early pediatric atopic dermatitis shows only a cutaneous lymphocyte antigen (CLA)(+) TH2/TH1 cell imbalance, whereas adults acquire CLA(+) TH22/TC22 cell subsets J. Allergy Clin. Immunol. 2015 136 941 951.e3 10.1016/j.jaci.2015.05.049 26242300 PMC4946641 · DOI
  68. [79]Suárez-Fariñas M. Dhingra N. Gittler J. Shemer A. Cardinale I. de Guzman Strong C. Krueger J.G. Guttman-Yassky E. Intrinsic atopic dermatitis shows similar TH2 and higher TH17 immune activation compared with extrinsic atopic dermatitis J. Allergy Clin. Immunol. 2013 132 361 370 10.1016/j.jaci.2013.04.046 23777851 PMC3991240 · DOI · Paper page
  69. [80]Witte E. Kokolakis G. Witte K. Philipp S. Doecke W.D. Babel N. Wittig B.M. Warszawska K. Kurek A. Erdmann-Keding M. IL-19 is a component of the pathogenetic IL-23/IL-17 cascade in psoriasis J Investig. Dermatol. 2014 134 2757 2767 10.1038/jid.2014.308 25046339 · DOI
  70. [81]Huang F. Wachi S. Thai P. Loukoianov A. Tan K.H. Forteza R.M. Wu R. Potentiation of IL-19 expression in airway epithelia by IL-17A and IL-4/IL-13: Important implications in asthma J. Allergy Clin. Immunol. 2008 121 1415 1421 10.1016/j.jaci.2008.04.016 18539194 PMC4631388 · DOI
  71. [82]Tokura Y. Extrinsic and intrinsic types of atopic dermatitis J. Dermatol Sci. 2010 58 1 7 10.1016/j.jdermsci.2010.02.008 20207111 · DOI
  72. [83]Tanei R. Clinical Characteristics, Treatments, and Prognosis of Atopic Eczema in the Elderly J. Clin. Med. 2015 18 979 997 10.3390/jcm4050979 26239460 PMC4470211 · DOI
  73. [84]Zhou L. Leonard A. Pavel A.B. Malik K. Raja A. Glickman J. Estrada Y.D. Peng X. Del Duca E. Sanz-Cabanillas J. Age-specific changes in the molecular phenotype of patients with moderate-to-severe atopic dermatitis J. Allergy Clin. Immunol. 2019 144 144 156 10.1016/j.jaci.2019.01.015 30685456 · DOI · Paper page
  74. [85]Bozek A. Fisher A. Filipowska B. Mazur B. Jarzab J. Clinical features and immunological markers of atopic dermatitis in elderly patients Int. Arch. Allergy Immunol. 2012 157 372 378 10.1159/000329150 22122980 · DOI
  75. [86]Muraro A. Lemanske R.F. Jr. Hellings P.W. Akdis C.A. Bieber T. Casale T.B. Jutel M. Ong P.Y. Poulsen L.K. Schmid-Grendelmeier P. Precision medicine in patients with allergic diseases: Airway diseases and atopic dermatitis-PRACTALL document of the European Academy of Allergy and Clinical Immunology and the American Academy of Allergy, Asthma & Immunology J. Allergy Clin. Immunol. 2016 137 1347 1358 10.1016/j.jaci.2016.03.010 27155030 · DOI
  76. [87]Brunner P.M. Silverberg J.I. Guttman-Yassky E. Paller A.S. Kabashima K. Amagai M. Luger T.A. Deleuran M. Werfel T. Eyerich K. Councilors of the International Eczema Council. Increasing Comorbidities Suggest that Atopic Dermatitis Is a Systemic Disorder J. Investig. Dermatol. 2017 137 18 25 10.1016/j.jid.2016.08.022 27771048 · DOI
  77. [88]Oliveira C. Torres T. More than skin deep: The systemic nature of atopic dermatitis Eur. J. Dermatol. 2019 29 250 258 10.1684/ejd.2019.3557 31122909 · DOI
  78. [89]Leung D.Y. Harbeck R. Bina P. Reiser R.F. Yang E. Norris D.A. Hanifin J.M. Sampson H.A. Presence of IgE antibodies to staphylococcal exotoxins on the skin of patients with atopic dermatitis. Evidence for a new group of allergens J. Clin. Investig. 1993 2 1374 1380 10.1172/JCI116711 PMC288279 7690780 · DOI
  79. [90]Totté J. de Wit J. Pardo L. Schuren F. van Doorn M. Pasmans S. Targeted anti-staphylococcal therapy with endolysins in atopic dermatitis and the effect on steroid use, disease severity and the microbiome: Study protocol for a randomized controlled trial (MAAS trial) Trials 2017 18 404 10.1186/s13063-017-2118-x 28859690 PMC5580294 · DOI
  80. [91]Schmid-Grendelmeier P. Flückiger S. Disch R. Trautmann A. Wüthrich B. Blaser K. Scheynius A. Crameri R. IgE-mediated and T cell-mediated autoimmunity against manganese superoxide dismutase in atopic dermatitis J. Allergy Clin. Immunol. 2005 115 1068 1075 10.1016/j.jaci.2005.01.065 15867868 · DOI
  81. [92]Flückiger S. Scapozza L. Mayer C. Blaser K. Folkers G. Crameri R. Immunological and structural analysis of IgE-mediated cross-reactivity between manganese superoxide dismutases Int. Arch. Allergy Immunol. 2002 128 292 303 10.1159/000063862 12218367 · DOI
  82. [93]Scala E. Abeni D. Guerra E.C. Pirrotta L. Locanto M. Meneguzzi G. Giani M. Russo G. Asero R. β-1,3-glucanase rOle e 9 and MnSOD rAsp f 6 IgE reactivity are the signature of atopic dermatitis in the Mediterranean area Clin. Exp. Allergy 2020 50 487 498 10.1111/cea.13555 31885112 · DOI
  83. [94]Valenta R. Mittermann I. Werfel T. Garn H. Renz H. Linking allergy to autoimmune disease Trends Immunol. 2009 30 109 116 10.1016/j.it.2008.12.004 19231288 · DOI
  84. [95]Valenta R. Natter S. Seiberler S. Wichlas S. Maurer D. Hess M. Pavelka M. Grote M. Ferreira F. Szepfalusi Z. Molecular characterization of an autoallergen, Hom s 1, identified by serum IgE from atopic dermatitis patients J. Investig. Dermatol. 1998 111 1178 1183 10.1046/j.1523-1747.1998.00413.x 9856836 · DOI
  85. [96]Mittermann I. Reininger R. Zimmermann M. Gangl K. Reisinger J. Aichberger K.J. Greisenegger E.K. Niederberger V. Seipelt J. Bohle B. The IgE-reactive autoantigen Hom s 2 induces damage of respiratory epithelial cells and keratinocytes via induction of IFN-gamma J. Investig. Dermatol. 2008 128 1451 1459 10.1038/sj.jid.5701195 18079747 · DOI
  86. [97]Aichberger K.J. Mittermann I. Reininger R. Seiberler S. Swoboda I. Spitzauer S. Kopp T. Stingl G. Sperr W.R. Valent P. Hom s 4, an IgE-reactive autoantigen belonging to a new subfamily of calcium-binding proteins, can induce Th cell type 1-mediated autoreactivity J. Immunol. 2005 175 1286 1294 10.4049/jimmunol.175.2.1286 16002733 · DOI
  87. [98]Dzoro S. Mittermann I. Resch-Marat Y. Vrtala S. Nehr M. Hirschl A.M. Wikberg G. Lundeberg L. Johansson C. Scheynius A. House dust mites as potential carriers for IgE sensitization to bacterial antigens Allergy 2018 73 115 124 10.1111/all.13260 28741705 PMC5763376 · DOI
  88. [99]Nguyen H.L.T. Trujillo-Paez J.V. Umehara Y. Yue H. Peng G. Kiatsurayanon C. Chieosilapatham P. Song P. Okumura K. Ogawa H. Role of Antimicrobial Peptides in Skin Barrier Repair in Individuals with Atopic Dermatitis Int. J. Mol. Sci. 2020 21 7607 10.3390/ijms21207607 PMC7589391 33066696 · DOI
  89. [100]Niyonsaba F. Kiatsurayanon C. Chieosilapatham P. Ogawa H. Friends or Foes? Host defense (antimicrobial) peptides and proteins in human skin diseases Exp. Dermatol. 2017 26 989 998 10.1111/exd.13314 28191680 · DOI
  90. [101]Pahar B. Madonna S. Das A. Albanesi C. Girolomoni G. Immunomodulatory Role of the Antimicrobial LL-37 Peptide in Autoimmune Diseases and Viral Infections Vaccines 2020 8 517 10.3390/vaccines8030517 32927756 PMC7565865 · DOI
  91. [102]Reinholz M. Ruzicka T. Schauber J. Cathelicidin LL-37: An antimicrobial peptide with a role in inflammatory skin disease Ann. Dermatol. 2012 24 126 135 10.5021/ad.2012.24.2.126 22577261 PMC3346901 · DOI
  92. [103]Akiyama T. Niyonsaba F. Kiatsurayanon C. Nguyen T.T. Ushio H. Fujimura T. Ueno T. Okumura K. Ogawa H. Ikeda S.J. The human cathelicidin LL-37 host defense peptide upregulates tight junction-related proteins and increases human epidermal keratinocyte barrier function Innate Immun. 2014 6 739 753 10.1159/000362789 24862212 PMC6742956 · DOI
  93. [104]Lee H. Ryu W.I. Kim H.J. Bae H.C. Ryu H.J. Shin J.J. Song K.H. Kim T.W. Son S.W. TSLP Down-Regulates S100A7 and ß-Defensin 2 Via the JAK2/STAT3-Dependent Mechanism J. Investig. Dermatol. 2016 136 2427 2435 10.1016/j.jid.2016.07.027 27498343 · DOI
  94. [105]Hänel K.H. Pfaff C.M. Cornelissen C. Amann P.M. Marquardt Y. Czaja K. Kim A. Lüscher B. Baron J.M. Control of the Physical and Antimicrobial Skin Barrier by an IL-31-IL-1 Signaling Network J. Immunol. 2016 196 3233 3244 10.4049/jimmunol.1402943 26944931 · DOI
  95. [106]Fenner J. Silverberg N.B. Skin diseases associated with atopic dermatitis Clin. Dermatol. 2018 36 631 640 10.1016/j.clindermatol.2018.05.004 30217275 · DOI
  96. [107]Owen J.L. Vakharia P.P. Silverberg J.I. The Role and Diagnosis of Allergic Contact Dermatitis in Patients with Atopic Dermatitis Am. J. Clin. Dermatol. 2018 19 293 302 10.1007/s40257-017-0340-7 29305764 PMC5948135 · DOI · Paper page
  97. [108]Gutin L. Tammaro A. Fishelevich R. Gaspari A.A. Elevation of IL-9 in Extreme Patch Test Reactions Suggests It Is an Inflammatory Mediator in Allergic Contact Dermatitis Dermatitis 2016 27 35 36 10.1097/DER.0000000000000159 26756516 · DOI
  98. [109]Koga C. Kabashima K. Shiraishi N. Kobayashi M. Tokura Y. Possible pathogenic role of Th17 cells for atopic dermatitis J. Investig. Dermatol. 2008 128 2625 2630 10.1038/jid.2008.111 18432274 · DOI
  99. [110]Nakae S. Komiyama Y. Nambu A. Sudo K. Iwase M. Homma I. Sekikawa K. Asano M. Iwakura Y. Antigen-specific T cell sensitization is impaired in IL-17-deficient mice, causing suppression of allergic cellular and humoral responses Immunity 2002 17 375 387 10.1016/S1074-7613(02)00391-6 12354389 · DOI
  100. [111]Milam E.C. Jacob S.E. Cohen D.E. Contact Dermatitis in the Patient with Atopic Dermatitis J. Allergy Clin. Immunol. Pract. 2019 7 18 26 10.1016/j.jaip.2018.11.003 30598176 · DOI
  101. [112]Hamann C.R. Hamann D. Egeberg A. Johansen J.D. Silverberg J. Thyssen J.P. Association between atopic dermatitis and contact sensitization: A systematic review and meta-analysis J. Am. Acad. Dermatol. 2017 77 70 78 10.1016/j.jaad.2017.02.001 28392290 · DOI
  102. [113]Ivert L.U. Wahlgren C.F. Lindelöf B. Dal H. Bradley M. Johansson E.K. Association between atopic dermatitis and autoimmune diseases: A population-based case-control study Br. J. Dermatol. 2021 185 335 342 10.1111/bjd.19624 33091150 PMC8451742 · DOI
  103. [114]Kusari A. Han A.M. Schairer D. Eichenfield L.F. Atopic Dermatitis: New Developments Dermatol. Clin. 2019 37 11 20 10.1016/j.det.2018.07.003 30466683 · DOI
  104. [115]Yaghmaie P. Koudelka C.W. Simpson E.L. Mental health comorbidity in patients with atopic dermatitis J. Allergy Clin. Immunol. 2013 131 428 433 10.1016/j.jaci.2012.10.041 23245818 PMC3565469 · DOI · Paper page
  105. [116]Sampogna F. Tabolli S. Abeni D. Impact of different skin conditions on quality of life G. Ital. Dermatol. Venereol. 2013 148 255 261 23670062
  106. [117]Gómez R.L. Edgin J.O. Sleep as a window into early neural development: Shifts in sleep-dependent learning effects across early childhood Child Dev. Perspect. 2015 9 183 189 10.1111/cdep.12130 26557155 PMC4636128 · DOI · Paper page
  107. [118]Paller A. Jaworski J.C. Simpson E.L. Boguniewicz M. Russell J.J. Block J.K. Tofte S. Dunn J.D. Feldman S.R. Clark A.R. Major Comorbidities of Atopic Dermatitis: Beyond Allergic Disorders Am. J. Clin. Dermatol. 2018 19 821 838 10.1007/s40257-018-0383-4 30168085 · DOI
  108. [119]Vajdic C.M. Falster M.O. de Sanjose S. Martínez-Maza O. Becker N. Bracci P.M. Melbye M. Smedby K.E. Engels E.A. Turner J. Atopic disease and risk of non-Hodgkin lymphoma: An InterLymph pooled analysis Cancer Res. 2009 69 6482 6489 10.1158/0008-5472.CAN-08-4372 19654312 PMC2758272 · DOI
  109. [120]Brunner P.M. Suárez-Fariñas M. He H. Malik K. Wen H.C. Gonzalez J. Chan T.C. Estrada Y. Zheng X. Khattri S. The atopic dermatitis blood signature is characterized by increases in inflammatory and cardiovascular risk proteins Sci. Rep. 2017 18 8707 10.1038/s41598-017-09207-z PMC5562859 28821884 · DOI
  110. [121]Ständer S. Atopic Dermatitis N. Engl. J. Med. 2021 384 1136 1143 10.1056/NEJMra2023911 33761208 · DOI
  111. [122]Wollenberg A. Barbarot S. Bieber T. Christen-Zaech S. Deleuran M. Fink-Wagner A. Gieler U. Girolomoni G. Lau S. Muraro A. Consensus-based European guidelines for treatment of atopic eczema (atopic dermatitis) in adults and children: Part I J. Eur. Acad. Dermatol. Venereol. 2018 32 657 682 10.1111/jdv.14891 29676534 · DOI · Paper page
  112. [123]Ahn J. Choi Y. Simpson E.L. Therapeutic New Era for Atopic Dermatitis: Part 1. Biologics Ann. Dermatol. 2021 33 1 10 10.5021/ad.2021.33.1.1 33911806 PMC7875213 · DOI
  113. [124]Wollenberg A. Barbarot S. Bieber T. Christen-Zaech S. Deleuran M. Fink-Wagner A. Gieler U. Girolomoni G. Lau S. Muraro A. Consensus-based European guidelines for treatment of atopic eczema (atopic dermatitis) in adults and children: Part II J. Eur. Acad. Dermatol. Venereol. 2018 32 850 878 10.1111/jdv.14888 29878606 · DOI · Paper page
  114. [125]Senner S. Seegräber M. Frey S. Kendziora B. Eicher L. Wollenberg A. Dupilumab for the treatment of adolescents with atopic dermatitis Expert Rev. Clin. Immunol. 2020 16 641 650 10.1080/1744666X.2020.1801420 32720530 · DOI
  115. [126]Chen Y.L. Gutowska-Owsiak D. Hardman C.S. Westmoreland M. MacKenzie T. Cifuentes L. Waithe D. Lloyd-Lavery A. Marquette A. Londei M. Proof-of-concept clinical trial of etokimab shows a key role for IL-33 in atopic dermatitis pathogenesis Transl. Med. 2019 11 eaax2945 10.1126/scitranslmed.aax2945 31645451 · DOI · Paper page
  116. [127]Traidl S. Freimooser S. Werfel T. Janus kinase inhibitors for the therapy of atopic dermatitis Allergol. Select 2021 27 293 304 10.5414/ALX02272E PMC8439108 34532638 · DOI
  117. [128]Spinelli F.R. Meylan F. O’Shea J.J. Gadina M. JAK inhibitors: Ten years after Eur. J. Immunol. 2021 51 1615 1627 10.1002/eji.202048922 33930196 · DOI
  118. [129]Markham A. Keam S.J. Peficitinib: First Global Approval Drugs 2019 79 887 891 10.1007/s40265-019-01131-y 31093950 · DOI
  119. [130]Blauvelt A. Teixeira H.D. Simpson E.L. Costanzo A. De Bruin-Weller M. Barbarot S. Prajapati V.H. Lio P. Hu X. Wu T. Efficacy and Safety of Upadacitinib vs Dupilumab in Adults With Moderate-to-Severe Atopic Dermatitis: A Randomized Clinical Trial JAMA Dermatol. 2021 157 1047 1055 10.1001/jamadermatol.2021.3023 34347860 PMC8340015 · DOI · Paper page

Cited by

Sorted by citations

Authors
Fania, L., Moretta, G., Antonelli, F., Scala, E., Abeni, D., Albanesi, C., & Madonna, S.
Affiliations
Istituto Dermopatico dell'Immacolata (IT)
Corresponding author
Albanesi, Cristina
ORCID
Venue
International Journal of Molecular Sciences
Publisher
MDPI AG
Published
2022-02-28
Volume
23
Issue
5
Pages
2684
ISSN
1422-0067 (ISSN-L)
DOI
10.3390/ijms23052684
PMC
PMC8910412
OpenAlex
W4214638324
Cited by
128
References
11
Citations by year
2026: 28 · 2025: 42 · 2024: 36 · 2023: 14 · 2022: 8
FWCI
4.45
Type
journal article
Language
en
Open access
Licence
Locations
  • International Journal of Molecular Sciences (publishedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
Funders
Ministero della Salute
Topics
  • Health Sciences › Medicine › Dermatology › Dermatology and Skin Diseases
  • Health Sciences › Medicine › Dermatology › Contact Dermatitis and Allergies
  • Health Sciences › Medicine › Physiology › Asthma and respiratory diseases
Keywords
atopic dermatitis, cytokines, disease endotypes, biomarkers, adult-onset atopic dermatitis, filaggrin mutations, skin barrier dysfunction, type 2 inflammation, Langerhans cells, dendritic cells, IgE sensitization, biologic therapy, personalized treatment, pruritus
MeSH terms
Dermatitis, Atopic, Humans, Immunoglobulin E, Pruritus, Skin Diseases, Biomarkers, Cytokines

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