Skip to main content

Advertisement

SpringerLink
Log in

Implication of T Helper Cytokines in Contact Dermatitis and Atopic Dermatitis

  • Contact Dermatitis (A Gimenez-Arnau, Section Editor)
  • Published:
Current Treatment Options in Allergy Aims and scope Submit manuscript

Abstract

Purpose of review

Cytokines play a key role in lesion development in inflammatory skin diseases such as contact dermatitis and atopic dermatitis and are of great interest as therapeutic targets. This is reflected in the increasing number of clinical studies and case reports as well as preclinical mouse models that provide substantial data on the participation of cytokines in these pathologies. In this review, we provide a detailed and comprehensive account of the advances in the field.

Recent results

The importance and therapeutic potential of Th2 cytokines in allergic contact dermatitis (ACD) and atopic dermatitis (AD) are well documented. Recent results have added another member, IL-24, to the list of key players in both diseases. In addition, IL-9, which is associated with Th9 cells, has been found to be strongly increased in ACD patients, opening up another promising new avenue.

Summary

In this review, we describe the expression and role of Th cytokines in skin inflammatory disorders, based on mouse models and existing therapy, focusing on cytokines associated with different subpopulations of T helper cells.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References and Recommended Reading

Papers of particular interest, published recently, have been highlighted as: • Of importance •• Of major importance

  1. Tan CH, Rasool S, Johnston GA. Contact dermatitis: allergic and irritant. Clin Dermatol. 2014;32(1):116–24.

    PubMed  Google Scholar 

  2. Lee HY, Stieger M, Yawalkar N, Kakeda M. Cytokines and chemokines in irritant contact dermatitis. Mediat Inflamm. 2013;2013:916497.

    Google Scholar 

  3. Luckett-Chastain LR, Gipson JR, Gillaspy AF, Gallucci RM. Transcriptional profiling of irritant contact dermatitis (ICD) in a mouse model identifies specific patterns of gene expression and immune-regulation. Toxicology. 2018;410:1–9.

    CAS  PubMed  Google Scholar 

  4. Wood LC, Elias PM, Calhoun C, Tsai JC, Grunfeld C, Feingold KR. Barrier disruption stimulates interleukin-1 alpha expression and release from a pre-formed pool in murine epidermis. J Invest Dermatol. 1996;106(3):397–403.

    CAS  PubMed  Google Scholar 

  5. Corsini E, Galli CL. Cytokines and irritant contact dermatitis. Toxicol Lett. 1998;102–103:277–82.

    PubMed  Google Scholar 

  6. Ho KK, Campbell KL, Lavergne SN. Contact dermatitis: a comparative and translational review of the literature. Vet Dermatol. 2015;26(5):314–27 e66-7.

    PubMed  Google Scholar 

  7. •• Bains SN, Nash P, Fonacier L. Irritant contact dermatitis. Clin Rev Allergy Immunol. 2019;56(1):99–109 A good review providing an overview of the clinical aspects of ICD.

  8. Lee EG, Mickle-Kawar BM, Gallucci RM. IL-6 deficiency exacerbates skin inflammation in a murine model of irritant dermatitis. J Immunotoxicol. 2013;10(2):192–200.

    CAS  PubMed  Google Scholar 

  9. Frempah B, Luckett-Chastain LR, Calhoun KN, Gallucci RM. Keratinocyte-specific deletion of the IL-6RAlpha exacerbates the inflammatory response during irritant contact dermatitis. Toxicology. 2019;423:123–31.

    CAS  PubMed  Google Scholar 

  10. Frempah B, Luckett-Chastain LR, Gallucci RM. IL6Ralpha function in myeloid cells modulates the inflammatory response during irritant contact dermatitis. Exp Dermatol. 2019;28(8):948–55.

    CAS  PubMed  Google Scholar 

  11. Landeck L, Visser M, Kezic S, John SM. IL1A-889 C/T gene polymorphism in irritant contact dermatitis. J Eur Acad Dermatol Venereol. 2013;27(8):1040–3.

    CAS  PubMed  Google Scholar 

  12. Allen MH, Wakelin SH, Holloway D, Lisby S, Baadsgaard O, Barker JN, et al. Association of TNFA gene polymorphism at position −308 with susceptibility to irritant contact dermatitis. Immunogenetics. 2000;51(3):201–5.

    CAS  PubMed  Google Scholar 

  13. Landeck L, Visser M, Kezic S, John SM. Impact of tumour necrosis factor-alpha polymorphisms on irritant contact dermatitis. Contact Dermatitis. 2012;66(4):221–7.

    CAS  PubMed  Google Scholar 

  14. Piguet PF, Grau GE, Hauser C, Vassalli P. Tumor necrosis factor is a critical mediator in hapten induced irritant and contact hypersensitivity reactions. J Exp Med. 1991;173(3):673–9.

    CAS  PubMed  Google Scholar 

  15. Hoefakker S, Caubo M, van ’t Erve EH, Roggeveen MJ, Boersma WJ, van Joost T, et al. In vivo cytokine profiles in allergic and irritant contact dermatitis. Contact Dermatitis. 1995;33(4):258–66.

    CAS  PubMed  Google Scholar 

  16. Zhang L, Tinkle SS. Chemical activation of innate and specific immunity in contact dermatitis. J Invest Dermatol. 2000;115(2):168–76.

    CAS  PubMed  Google Scholar 

  17. Bonneville M, Chavagnac C, Vocanson M, Rozieres A, Benetiere J, Pernet I, et al. Skin contact irritation conditions the development and severity of allergic contact dermatitis. J Invest Dermatol. 2007;127(6):1430–5.

    CAS  PubMed  Google Scholar 

  18. Calhoun KN, Luckett-Chastain LR, Frempah B, Gallucci RM. Associations between immune phenotype and inflammation in murine models of irritant contact dermatitis. Toxicol Sci. 2019;168(1):179–89.

    CAS  PubMed  Google Scholar 

  19. Simon D, Aeberhard C, Erdemoglu Y, Simon HU. Th17 cells and tissue remodeling in atopic and contact dermatitis. Allergy. 2014;69(1):125–31.

    CAS  PubMed  Google Scholar 

  20. • Dai J, Choo MK, Park JM, Fisher DE. Topical ROR Inverse agonists suppress inflammation in mouse models of atopic dermatitis and acute irritant dermatitis. J Invest Dermatol. 2017;137(12):2523–31 This paper demonstrates the protective effect of RORa/g inverse agonists on ICD.

  21. • Frempah B, Luckett-Chastain LR, Gallucci RM. IL-6 negatively regulates IL-22Ralpha expression on epidermal keratinocytes: implications for irritant contact dermatitis. J Immunol Res. 2019;2019:6276254 The paper describing the potential involvement of IL-22 in ICD.

  22. Amano W, Nakajima S, Yamamoto Y, Tanimoto A, Matsushita M, Miyachi Y, et al. JAK inhibitor JTE-052 regulates contact hypersensitivity by downmodulating T cell activation and differentiation. J Dermatol Sci. 2016;84(3):258–65.

    CAS  PubMed  Google Scholar 

  23. •• Koppes SA, Engebretsen KA, Agner T, Angelova-Fischer I, Berents T, Brandner J, et al. current knowledge on biomarkers for contact sensitization and allergic contact dermatitis. Contact Dermatitis. 2017;77(1):1–16 Nice review on the pathogenesis of ACD.

  24. Peiser M, Tralau T, Heidler J, Api AM, Arts JH, Basketter DA, et al. Allergic contact dermatitis: epidemiology, molecular mechanisms, in vitro methods and regulatory aspects. Current knowledge assembled at an international workshop at BfR, Germany. Cell Mol Life Sci. 2012;69(5):763–81.

    CAS  PubMed  Google Scholar 

  25. Martins LE, Reis VM. Immunopathology of allergic contact dermatitis. An Bras Dermatol. 2011;86(3):419–33.

    PubMed  Google Scholar 

  26. Posadas SJ, Pichler WJ. Delayed drug hypersensitivity reactions - new concepts. Clin Exp Allergy. 2007;37(7):989–99.

    CAS  PubMed  Google Scholar 

  27. Pichler WJ. Delayed drug hypersensitivity reactions. Ann Intern Med. 2003;139(8):683–93.

    CAS  PubMed  Google Scholar 

  28. Mori T, Kabashima K, Yoshiki R, Sugita K, Shiraishi N, Onoue A, et al. Cutaneous hypersensitivities to hapten are controlled by IFN-gamma-upregulated keratinocyte Th1 chemokines and IFN-gamma-downregulated langerhans cell Th2 chemokines. J Invest Dermatol. 2008;128(7):1719–27.

    CAS  PubMed  Google Scholar 

  29. He D, Wu L, Kim HK, Li H, Elmets CA, Xu H. IL-17 and IFN-gamma mediate the elicitation of contact hypersensitivity responses by different mechanisms and both are required for optimal responses. J Immunol. 2009;183(2):1463–70.

    CAS  PubMed  PubMed Central  Google Scholar 

  30. Yokozeki H, Ghoreishi M, Takagawa S, Takayama K, Satoh T, Katayama I, et al. Signal transducer and activator of transcription 6 is essential in the induction of contact hypersensitivity. J Exp Med. 2000;191(6):995–1004.

    CAS  PubMed  PubMed Central  Google Scholar 

  31. Honda T, Egawa G, Grabbe S, Kabashima K. Update of immune events in the murine contact hypersensitivity model: toward the understanding of allergic contact dermatitis. J Invest Dermatol. 2013;133(2):303–15.

    CAS  PubMed  Google Scholar 

  32. Kunz S, Wolk K, Witte E, Witte K, Doecke WD, Volk HD, et al. Interleukin (IL)-19, IL-20 and IL-24 are produced by and act on keratinocytes and are distinct from classical ILs. Exp Dermatol. 2006;15(12):991–1004.

    CAS  PubMed  Google Scholar 

  33. Fujimoto Y, Fujita T, Kuramoto N, Kuwamura M, Izawa T, Nishiyama K, et al. The role of Interleukin-19 in contact hypersensitivity. Biol Pharm Bull. 2018;41(2):182–9.

    CAS  PubMed  Google Scholar 

  34. Jin H, He R, Oyoshi M, Geha RS. Animal models of atopic dermatitis. J Invest Dermatol. 2009;129(1):31–40.

    CAS  PubMed  PubMed Central  Google Scholar 

  35. Jiang X, Park CO, Geddes Sweeney J, Yoo MJ, Gaide O, Kupper TS. Dermal gammadelta T cells do not freely re-circulate out of skin and produce IL-17 to promote neutrophil infiltration during primary contact hypersensitivity. PLoS One. 2017;12(1):e0169397.

    PubMed  PubMed Central  Google Scholar 

  36. Matsushita A, Seike M, Hagiwara T, Sato A, Ohtsu H. Close relationship between T helper (Th)17 and Th2 response in murine allergic contact dermatitis. Clin Exp Dermatol. 2014;39(8):924–31.

    CAS  PubMed  Google Scholar 

  37. Nakae S, Komiyama Y, Nambu A, Sudo K, Iwase M, Homma I, et al. Antigen-specific T cell sensitization is impaired in IL-17-deficient mice, causing suppression of allergic cellular and humoral responses. Immunity. 2002;17(3):375–87.

    CAS  PubMed  Google Scholar 

  38. Ahlstrom MG, Thyssen JP, Wennervaldt M, Menne T, Johansen JD. Nickel allergy and allergic contact dermatitis: a clinical review of immunology, epidemiology, exposure, and treatment. Contact Dermatitis. 2019;81(4):227–41.

    PubMed  Google Scholar 

  39. Sinigaglia F, Scheidegger D, Garotta G, Scheper R, Pletscher M, Lanzavecchia A. Isolation and characterization of Ni-specific T cell clones from patients with Ni-contact dermatitis. J Immunol. 1985;135(6):3929–32.

    CAS  PubMed  Google Scholar 

  40. Minang JT, Arestrom I, Troye-Blomberg M, Lundeberg L, Ahlborg N. Nickel, cobalt, chromium, palladium and gold induce a mixed Th1- and Th2-type cytokine response in vitro in subjects with contact allergy to the respective metals. Clin Exp Immunol. 2006;146(3):417–26.

    CAS  PubMed  PubMed Central  Google Scholar 

  41. Minang JT, Troye-Blomberg M, Lundeberg L, Ahlborg N. Nickel elicits concomitant and correlated in vitro production of Th1-, Th2-type and regulatory cytokines in subjects with contact allergy to nickel. Scand J Immunol. 2005;62(3):289–96.

    CAS  PubMed  Google Scholar 

  42. Rustemeyer T, von Blomberg BM, van Hoogstraten IM, Bruynzeel DP, Scheper RJ. Analysis of effector and regulatory immune reactivity to nickel. Clin Exp Allergy. 2004;34(9):1458–66.

    CAS  PubMed  Google Scholar 

  43. Falsafi-Amin H, Lundeberg L, Bakhiet M, Nordlind K. Early DNA synthesis and cytokine expression in the nickel activation of peripheral blood mononuclear cells in nickel-allergic subjects. Int Arch Allergy Immunol. 2000;123(2):170–6.

    CAS  PubMed  Google Scholar 

  44. Probst P, Kuntzlin D, Fleischer B. TH2-type infiltrating T cells in nickel-induced contact dermatitis. Cell Immunol. 1995;165(1):134–40.

    CAS  PubMed  Google Scholar 

  45. Larsen JM, Bonefeld CM, Poulsen SS, Geisler C, Skov L. IL-23 and T(H)17-mediated inflammation in human allergic contact dermatitis. J Allergy Clin Immunol. 2009;123(2):486–92.

    CAS  PubMed  Google Scholar 

  46. Ricciardi L, Minciullo PL, Saitta S, Trombetta D, Saija A, Gangemi S. Increased serum levels of IL-22 in patients with nickel contact dermatitis. Contact Dermatitis. 2009;60(1):57–8.

    PubMed  Google Scholar 

  47. Caiazzo G, Di Caprio R, Lembo S, Raimondo A, Scala E, Patruno C, et al. IL-26 in allergic contact dermatitis: resource in a state of readiness. Exp Dermatol. 2018;27(6):681–4.

    CAS  PubMed  Google Scholar 

  48. Liu J, Harberts E, Tammaro A, Girardi N, Filler RB, Fishelevich R, et al. IL-9 regulates allergen-specific Th1 responses in allergic contact dermatitis. J Invest Dermatol. 2014;134(7):1903–11.

    CAS  PubMed  PubMed Central  Google Scholar 

  49. Todberg T, Zachariae C, Krustrup D, Skov L. The effect of anti-IL-17 treatment on the reaction to a nickel patch test in patients with allergic contact dermatitis. Int J Dermatol. 2019;58(3):e58–61.

    PubMed  Google Scholar 

  50. Zhu GA, Chen JK, Chiou A, Ko J, Honari G. Repeat patch testing in a patient with allergic contact dermatitis improved on dupilumab. JAAD Case Rep. 2019;5(4):336–8.

    PubMed  PubMed Central  Google Scholar 

  51. Jacob SE, Sung CT, Machler BC. Dupilumab for systemic allergy syndrome with dermatitis. Dermatitis. 2019;30(2):164–7.

    PubMed  Google Scholar 

  52. Joshi SR, Khan DA. Effective use of dupilumab in managing systemic allergic contact dermatitis. Dermatitis. 2018;29(5):282–4.

    CAS  PubMed  Google Scholar 

  53. Dhingra N, Shemer A. Correa da Rosa J, Rozenblit M, Fuentes-Duculan J, Gittler JK, et al. Molecular profiling of contact dermatitis skin identifies allergen-dependent differences in immune response. J Allergy Clin Immunol. 2014;134(2):362–72.

    CAS  PubMed  Google Scholar 

  54. Goldminz AM, Scheinman PL. A case series of dupilumab-treated allergic contact dermatitis patients. Dermatol Ther. 2018;31(6):e12701.

    PubMed  Google Scholar 

  55. Todberg T, Zachariae C, Krustrup D, Skov L. The effect of treatment with anti-interleukin-17 in patients with allergic contact dermatitis. Contact Dermatitis. 2018;78(6):431–2.

    PubMed  Google Scholar 

  56. Diepgen TL, Ofenloch RF, Bruze M, Bertuccio P, Cazzaniga S, Coenraads PJ, et al. Prevalence of contact allergy in the general population in different European regions. Br J Dermatol. 2016;174(2):319–29.

    CAS  PubMed  Google Scholar 

  57. Herman A, Aerts O, de Montjoye L, Tromme I, Goossens A, Baeck M. Isothiazolinone derivatives and allergic contact dermatitis: a review and update. J Eur Acad Dermatol Venereol. 2019;33(2):267–76.

    CAS  PubMed  Google Scholar 

  58. Masjedi K, Ahlborg N, Gruvberger B, Bruze M, Karlberg AT. Methylisothiazolinones elicit increased production of both T helper (Th)1- and Th2-like cytokines by peripheral blood mononuclear cells from contact allergic individuals. Br J Dermatol. 2003;149(6):1172–82.

    CAS  PubMed  Google Scholar 

  59. Martinez-Mera C, Gonzalez MA, Hospital M, Turrion-Merino L. Isothiazolinones in paint as a cause of airborne contact dermatitis in a patient with psoriasis receiving anti-interleukin-17 therapy. Contact Dermatitis. 2019;80(5):328–9.

    PubMed  Google Scholar 

  60. Coulter EM, Jenkinson C, Farrell J, Lavergne SN, Pease C, White A, et al. Measurement of CD4+ and CD8+ T-lymphocyte cytokine secretion and gene expression changes in p-phenylenediamine allergic patients and tolerant individuals. J Invest Dermatol. 2010;130(1):161–74.

    CAS  PubMed  Google Scholar 

  61. • Van Belle AB, Cochez PM, de Heusch M, Pointner L, Opsomer R, Raynaud P, et al. IL-24 contributes to skin inflammation in para-phenylenediamine-induced contact hypersensitivity. Sci Rep. 2019;9(1):1852 This paper points out the role of IL-24 in PPD-induced ACD.

  62. • Baeck M, Herman A, de Montjoye L, Hendrickx E, Cheou P, Cochez PM, et al. Increased expression of interleukin-9 in patients with allergic contact dermatitis caused by p-phenylenediamine. Contact Dermatitis. 2018;79(6):346–55 This paper highlights the role of IL-9 in PPD-induced ACD.

  63. Yokozeki H, Wu MH, Sumi K, Igawa K, Miyazaki Y, Katayama I, et al. Th2 cytokines, IgE and mast cells play a crucial role in the induction of para-phenylenediamine-induced contact hypersensitivity in mice. Clin Exp Immunol. 2003;132(3):385–92.

    CAS  PubMed  PubMed Central  Google Scholar 

  64. Rothe H, Sarlo K, Scheffler H, Goebel C. The hair dyes PPD and PTD fail to induce a T(H)2 immune response following repeated topical application in BALB/c mice. J Immunotoxicol. 2011;8(1):46–55.

    CAS  PubMed  Google Scholar 

  65. Elyaman W, Bradshaw EM, Uyttenhove C, Dardalhon V, Awasthi A, Imitola J, et al. IL-9 induces differentiation of TH17 cells and enhances function of FoxP3+ natural regulatory T cells. Proc Natl Acad Sci U S A. 2009;106(31):12885–90.

    CAS  PubMed  PubMed Central  Google Scholar 

  66. • Aerts O, Herman A, Mowitz M, Bruze M, Goossens A. Isobornyl acrylate. Dermatitis. 2020; This is an interesting paper on the new allergen IBOA.

  67. Herman A, de Montjoye L, Tromme I, Goossens A, Baeck M. Allergic contact dermatitis caused by medical devices for diabetes patients: a review. Contact Dermatitis. 2018;79(6):331–5.

    PubMed  Google Scholar 

  68. Gittler JK, Krueger JG, Guttman-Yassky E. Atopic dermatitis results in intrinsic barrier and immune abnormalities: implications for contact dermatitis. J Allergy Clin Immunol. 2013;131(2):300–13.

    CAS  PubMed  Google Scholar 

  69. Palmer CN, Irvine AD, Terron-Kwiatkowski A, Zhao Y, Liao H, Lee SP, et al. Common loss-of-function variants of the epidermal barrier protein filaggrin are a major predisposing factor for atopic dermatitis. Nat Genet. 2006;38(4):441–6.

    CAS  PubMed  Google Scholar 

  70. Weidinger S, Illig T, Baurecht H, Irvine AD, Rodriguez E, Diaz-Lacava A, et al. Loss-of-function variations within the filaggrin gene predispose for atopic dermatitis with allergic sensitizations. J Allergy Clin Immunol. 2006;118(1):214–9.

    CAS  PubMed  Google Scholar 

  71. Oliva M, Renert-Yuval Y, Guttman-Yassky E. The ‘omics’ revolution: redefining the understanding and treatment of allergic skin diseases. Curr Opin Allergy Clin Immunol. 2016;16(5):469–76.

    CAS  PubMed  Google Scholar 

  72. Narozna B, Hoffmann A, Sobkowiak P, Schoneich N, Breborowicz A, Szczepankiewicz A. Polymorphisms in the interleukin 4, interleukin 4 receptor and interleukin 13 genes and allergic phenotype: a case control study. Adv Med Sci. 2016;61(1):40–5.

    PubMed  Google Scholar 

  73. Zheng T, Oh MH, Oh SY, Schroeder JT, Glick AB, Zhu Z. Transgenic expression of interleukin-13 in the skin induces a pruritic dermatitis and skin remodeling. J Invest Dermatol. 2009;129(3):742–51.

    CAS  PubMed  Google Scholar 

  74. Chan LS, Robinson N, Xu L. Expression of interleukin-4 in the epidermis of transgenic mice results in a pruritic inflammatory skin disease: an experimental animal model to study atopic dermatitis. J Invest Dermatol. 2001;117(4):977–83.

    CAS  PubMed  Google Scholar 

  75. Rangel SM, Paller AS. Bacterial colonization, overgrowth, and superinfection in atopic dermatitis. Clin Dermatol. 2018;36(5):641–7.

    PubMed  Google Scholar 

  76. • Silverberg JI, Yosipovitch G, Simpson EL, Kim BS, Wu JJ, Eckert L, et al. Dupilumab treatment results in early and sustained improvements in itch in adolescents and adults with moderate-to-severe atopic dermatitis: analysis of the randomized phase 3 studies SOLO 1 & SOLO 2, AD ADOL, and CHRONOS. J Am Acad Dermatol. 2020; Analysis of 4 randomized phase III clinical trials using dupilumab therapy with a total of 1505 patients characterized by moderate to severe AD.

  77. •• Wu J, Guttman-Yassky E. Efficacy of biologics in atopic dermatitis. Expert Opin Biol Ther. 2020;20(5):525–38 This paper reviews all recent biologics for AD and gives interesting expert opinion.

  78. Wollenberg A, Beck LA, Blauvelt A, Simpson EL, Chen Z, Chen Q, et al. Laboratory safety of dupilumab in moderate-to-severe atopic dermatitis: results from three phase III trials (LIBERTY AD SOLO 1, LIBERTY AD SOLO 2, LIBERTY AD CHRONOS). Br J Dermatol. 2019.

  79. Blauvelt A, de Bruin-Weller M, Gooderham M, Cather JC, Weisman J, Pariser D, et al. Long-term management of moderate-to-severe atopic dermatitis with dupilumab and concomitant topical corticosteroids (LIBERTY AD CHRONOS): a 1-year, randomised, double-blinded, placebo-controlled, phase 3 trial. Lancet. 2017;389(10086):2287–303.

    CAS  PubMed  Google Scholar 

  80. • Guttman-Yassky E, Bissonnette R, Ungar B, Suarez-Farinas M, Ardeleanu M, Esaki H, et al. Dupilumab progressively improves systemic and cutaneous abnormalities in patients with atopic dermatitis. J Allergy Clin Immunol. 2019;143(1):155–72 Transcriptomic study showing the change of gene signature following dupilumab therapy.

  81. Guttman-Yassky E, Blauvelt A, Eichenfield LF, Paller AS, Armstrong AW, Drew J, et al. Efficacy and safety of lebrikizumab, a high-affinity interleukin 13 inhibitor, in adults with moderate to severe atopic dermatitis: a phase 2b randomized clinical trial. JAMA Dermatol. 2020;156:411.

    PubMed  PubMed Central  Google Scholar 

  82. Wollenberg A, Howell MD, Guttman-Yassky E, Silverberg JI, Kell C, Ranade K, et al. Treatment of atopic dermatitis with tralokinumab, an anti-IL-13 mAb. J Allergy Clin Immunol. 2019;143(1):135–41.

    CAS  PubMed  Google Scholar 

  83. Simpson EL, Flohr C, Eichenfield LF, Bieber T, Sofen H, Taieb A, et al. Efficacy and safety of lebrikizumab (an anti-IL-13 monoclonal antibody) in adults with moderate-to-severe atopic dermatitis inadequately controlled by topical corticosteroids: a randomized, placebo-controlled phase II trial (TREBLE). J Am Acad Dermatol. 2018;78(5):863–71 e11.

    CAS  PubMed  Google Scholar 

  84. Furue K, Ito T, Tsuji G, Ulzii D, Vu YH, Kido-Nakahara M, et al. The IL-13-OVOL1-FLG axis in atopic dermatitis. Immunology. 2019;158(4):281–6.

    CAS  PubMed  Google Scholar 

  85. Myles IA, Fontecilla NM, Valdez PA, Vithayathil PJ, Naik S, Belkaid Y, et al. Signaling via the IL-20 receptor inhibits cutaneous production of IL-1beta and IL-17A to promote infection with methicillin-resistant Staphylococcus aureus. Nat Immunol. 2013;14(8):804–11.

    CAS  PubMed  PubMed Central  Google Scholar 

  86. Silverberg JI, Pinter A, Pulka G, Poulin Y, Bouaziz JD, Wollenberg A, et al. Phase 2B randomized study of nemolizumab in adults with moderate-to-severe atopic dermatitis and severe pruritus. J Allergy Clin Immunol. 2020;145(1):173–82.

    CAS  PubMed  Google Scholar 

  87. • Czarnowicki T, He H, Canter T, Han J, Lefferdink R, Erickson T, et al. Evolution of pathologic T-cell subsets in patients with atopic dermatitis from infancy to adulthood. J Allergy Clin Immunol. 2020;145(1):215–28 Beautiful study which compares immune reactions and cytokine production in patients with AD from infancy to adulthood. The study demonstrates unique cytokine signature according to ages and the need for specific therapies.

  88. • Brunner PM, Pavel AB, Khattri S, Leonard A, Malik K, Rose S, et al. Baseline IL-22 expression in patients with atopic dermatitis stratifies tissue responses to fezakinumab. J Allergy Clin Immunol. 2019;143(1):142–54 Transcriptomic and immunochemistry skin analysis from patients with moderate to severe AD, effect of anti-IL-22 antibody (Fezakinumab) treatment.

  89. Sugaya M. The role of Th17-related cytokines in atopic dermatitis. Int J Mol Sci. 2020;21(4).

  90. Kamijo H, Miyagaki T, Hayashi Y, Akatsuka T, Watanabe-Otobe S, Oka T, et al. Increased IL-26 expression promotes T helper type 17- and T helper type 2-associated cytokine production by keratinocytes in atopic dermatitis. J Invest Dermatol. 2020;140(3):636–44 e2.

  91. Noda S, Suarez-Farinas M, Ungar B, Kim SJ, de Guzman SC, Xu H, et al. The Asian atopic dermatitis phenotype combines features of atopic dermatitis and psoriasis with increased TH17 polarization. J Allergy Clin Immunol. 2015;136(5):1254–64.

    CAS  PubMed  Google Scholar 

  92. Nakajima S, Kitoh A, Egawa G, Natsuaki Y, Nakamizo S, Moniaga CS, et al. IL-17A as an inducer for Th2 immune responses in murine atopic dermatitis models. J Invest Dermatol. 2014;134(8):2122–30.

    CAS  PubMed  Google Scholar 

  93. Hayashida S, Uchi H, Moroi Y, Furue M. Decrease in circulating Th17 cells correlates with increased levels of CCL17, IgE and eosinophils in atopic dermatitis. J Dermatol Sci. 2011;61(3):180–6.

    CAS  PubMed  Google Scholar 

  94. Saeki H, Kabashima K, Tokura Y, Murata Y, Shiraishi A, Tamamura R, et al. Efficacy and safety of ustekinumab in Japanese patients with severe atopic dermatitis: a randomized, double-blind, placebo-controlled, phase II study. Br J Dermatol. 2017;177(2):419–27.

    CAS  PubMed  Google Scholar 

  95. Khattri S, Brunner PM, Garcet S, Finney R, Cohen SR, Oliva M, et al. Efficacy and safety of ustekinumab treatment in adults with moderate-to-severe atopic dermatitis. Exp Dermatol. 2017;26(1):28–35.

    CAS  PubMed  Google Scholar 

  96. Caldarola G, Pirro F, Di Stefani A, Talamonti M, Galluzzo M, D'Adamio S, et al. Clinical and histopathological characterization of eczematous eruptions occurring in course of anti IL-17 treatment: a case series and review of the literature. Expert Opin Biol Ther. 2020:1–8.

  97. Ishiuji Y, Umezawa Y, Asahina A, Fukuta H, Aizawa N, Yanaba K, et al. Exacerbation of atopic dermatitis symptoms by ustekinumab in psoriatic patients with elevated serum immunoglobulin E levels: report of two cases. J Dermatol. 2018;45(6):732–4.

    CAS  PubMed  Google Scholar 

  98. Ciprandi G, De Amici M, Giunta V, Marseglia A, Marseglia G. Serum interleukin-9 levels are associated with clinical severity in children with atopic dermatitis. Pediatr Dermatol. 2013;30(2):222–5.

    PubMed  Google Scholar 

  99. Namkung JH, Lee JE, Kim E, Park GT, Yang HS, Jang HY, 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(1):16–21.

    CAS  PubMed  Google Scholar 

  100. Ciechanowicz P, Rakowska A, Sikora M, Rudnicka L. JAK-inhibitors in dermatology: current evidence and future applications. J Dermatolog Treat. 2019;30(7):648–58.

    CAS  PubMed  Google Scholar 

  101. Nakagawa H, Nemoto O, Igarashi A, Saeki H, Kaino H, Nagata T. Delgocitinib ointment, a topical Janus kinase inhibitor, in adult patients with moderate to severe atopic dermatitis: a phase 3, randomized, double-blind, vehicle-controlled study and an open-label, long-term extension study. J Am Acad Dermatol. 2020;82(4):823–31.

    CAS  PubMed  Google Scholar 

  102. Napolitano M, Fabbrocini G, Cinelli E, Stingeni L, Patruno C. Profile of baricitinib and its potential in the treatment of moderate to severe atopic dermatitis: a short review on the emerging clinical evidence. J Asthma Allergy. 2020;13:89–94.

    CAS  PubMed  PubMed Central  Google Scholar 

  103. Guttman-Yassky E, Thaci D, Pangan AL, Hong HC, Papp KA, Reich K, et al. Upadacitinib in adults with moderate to severe atopic dermatitis: 16-week results from a randomized, placebo-controlled trial. J Allergy Clin Immunol. 2020;145(3):877–84.

    CAS  PubMed  Google Scholar 

  104. Gooderham MJ, Forman SB, Bissonnette R, Beebe JS, Zhang W, Banfield C, et al. Efficacy and safety of oral Janus kinase 1 inhibitor abrocitinib for patients with atopic dermatitis: a phase 2 randomized clinical trial. JAMA Dermatol. 2019;155:1371.

    PubMed  PubMed Central  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. de Duve Institute, Université Catholique de Louvain, Brussels, Belgium

    Perrine Cochez PhD, Mathilde Choteau PhD, Nisha Limaye PhD & Laure Dumoutier PhD

  2. Department of Dermatology, Cliniques universitaires Saint-Luc, Brussels, Belgium

    Marie Baeck MD, PhD

  3. Institut de Recherche Expérimentale et Clinique (IREC), Université Catholique de Louvain, Brussels, Belgium

    Marie Baeck MD, PhD

  4. de Duve Institute, Avenue Hippocrate 74, B-1200, Brussels, Belgium

    Laure Dumoutier PhD

Authors
  1. Perrine Cochez PhD
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Mathilde Choteau PhD
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Nisha Limaye PhD
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Marie Baeck MD, PhD
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Laure Dumoutier PhD
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Laure Dumoutier PhD.

Ethics declarations

Conflict of interest

Perrine Cochez declares that she has no conflict of interest. Mathilde Choteau declares that she has no conflict of interest. Nisha Limaye declares that she has no conflict of interest. Marie Baeck declares that she has no conflict of interest. Laure Dumoutier declares that she has no conflict of interest.

Human and animal rights and informed consent

This article does not contain any studies with human or animal subjects performed by any of the authors.

Additional information

Publisher’s Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

This article is part of the Topical Collection on Contact Dermatitis

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Cochez, P., Choteau, M., Limaye, N. et al. Implication of T Helper Cytokines in Contact Dermatitis and Atopic Dermatitis. Curr Treat Options Allergy 7, 258–273 (2020). https://doi.org/10.1007/s40521-020-00263-x

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s40521-020-00263-x

Keywords

Search

Navigation