Early-onset pediatric atopic dermatitis is TH2 but also TH17 polarized in skin

Hitokazu Esaki, Patrick M. Brunner, Yael Renert-Yuval, Tali Czarnowicki, Thy Huynh, Gary Tran, Sarah Lyon, Giselle Rodriguez, Supriya Immaneni, Donald B. Johnson, Bruce Bauer, Judilyn Fuentes-Duculan, Xiuzhong Zheng, Xiangyu Peng, Yeriel D. Estrada, Hui Xu, Christina de Guzman Strong, Mayte Suárez-Fariñas, James G. Krueger, Amy S. PallerEmma Guttman-Yassky

Research output: Contribution to journalArticle

102 Citations (Scopus)

Abstract

Background Atopic dermatitis (AD) affects 15% to 25% of children and 4% to 7% of adults. Paradigm-shifting discoveries about AD have been based on adult biomarkers, reflecting decades of disease activity, although 85% of cases begin by 5 years. Blood phenotyping shows only TH2 skewing in patients with early-onset pediatric AD, but alterations in early pediatric skin lesions are unknown, limiting advancement of targeted therapies. Objective We sought to characterize the early pediatric AD skin phenotype and its differences from pediatric control subjects and adults with AD. Methods Using immunohistochemistry and quantitative real-time PCR, we assessed biopsy specimens from 19 children with AD younger than 5 years within 6 months of disease onset in comparison with adults with AD or psoriasis and pediatric and adult control subjects. Results In lesional skin children showed comparable or greater epidermal hyperplasia (thickness and keratin 16) and cellular infiltration (CD3+, CD11c+, and FcεRI+) than adults with AD. Similar to adults, strong activation of the TH2 (IL-13, IL-31, and CCL17) and TH22 (IL-22 and S100As) axes and some TH1 skewing (IFN-γ and CXCL10) were present. Children showed significantly higher induction of TH17-related cytokines and antimicrobials (IL-17A, IL-19, CCL20, LL37, and peptidase inhibitor 3/elafin), TH9/IL-9, IL-33, and innate markers (IL-8) than adults (P < .02). Despite the characteristic downregulation in adult patients with AD, filaggrin expression was similar in children with AD and healthy children. Nonlesional skin in pediatric patients with AD showed higher levels of inflammation (particularly IL-17A and the related molecules IL-19 and LL37) and epidermal proliferation (keratin 16 and S100As) markers (P < .001). Conclusion The skin phenotype of new-onset pediatric AD is substantially different from that of adult AD. Although excess TH2 activation characterizes both, TH9 and TH17 are highly activated at disease initiation. Increases in IL-19 levels might link TH2 and TH17 activation.

Original languageEnglish
Pages (from-to)1639-1651
Number of pages13
JournalJournal of Allergy and Clinical Immunology
Volume138
Issue number6
DOIs
Publication statusPublished - Dec 1 2016

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Atopic Dermatitis
Pediatrics
Skin
Keratin-16
Interleukin-17
Elafin
Interleukin-9
Phenotype
Interleukin-13
Protease Inhibitors
Interleukin-8
Psoriasis
Hyperplasia
Real-Time Polymerase Chain Reaction
Down-Regulation
Biomarkers
Immunohistochemistry
Cytokines

All Science Journal Classification (ASJC) codes

  • Immunology and Allergy
  • Immunology

Cite this

Esaki, H., Brunner, P. M., Renert-Yuval, Y., Czarnowicki, T., Huynh, T., Tran, G., ... Guttman-Yassky, E. (2016). Early-onset pediatric atopic dermatitis is TH2 but also TH17 polarized in skin. Journal of Allergy and Clinical Immunology, 138(6), 1639-1651. https://doi.org/10.1016/j.jaci.2016.07.013

Early-onset pediatric atopic dermatitis is TH2 but also TH17 polarized in skin. / Esaki, Hitokazu; Brunner, Patrick M.; Renert-Yuval, Yael; Czarnowicki, Tali; Huynh, Thy; Tran, Gary; Lyon, Sarah; Rodriguez, Giselle; Immaneni, Supriya; Johnson, Donald B.; Bauer, Bruce; Fuentes-Duculan, Judilyn; Zheng, Xiuzhong; Peng, Xiangyu; Estrada, Yeriel D.; Xu, Hui; de Guzman Strong, Christina; Suárez-Fariñas, Mayte; Krueger, James G.; Paller, Amy S.; Guttman-Yassky, Emma.

In: Journal of Allergy and Clinical Immunology, Vol. 138, No. 6, 01.12.2016, p. 1639-1651.

Research output: Contribution to journalArticle

Esaki, H, Brunner, PM, Renert-Yuval, Y, Czarnowicki, T, Huynh, T, Tran, G, Lyon, S, Rodriguez, G, Immaneni, S, Johnson, DB, Bauer, B, Fuentes-Duculan, J, Zheng, X, Peng, X, Estrada, YD, Xu, H, de Guzman Strong, C, Suárez-Fariñas, M, Krueger, JG, Paller, AS & Guttman-Yassky, E 2016, 'Early-onset pediatric atopic dermatitis is TH2 but also TH17 polarized in skin', Journal of Allergy and Clinical Immunology, vol. 138, no. 6, pp. 1639-1651. https://doi.org/10.1016/j.jaci.2016.07.013
Esaki H, Brunner PM, Renert-Yuval Y, Czarnowicki T, Huynh T, Tran G et al. Early-onset pediatric atopic dermatitis is TH2 but also TH17 polarized in skin. Journal of Allergy and Clinical Immunology. 2016 Dec 1;138(6):1639-1651. https://doi.org/10.1016/j.jaci.2016.07.013
Esaki, Hitokazu ; Brunner, Patrick M. ; Renert-Yuval, Yael ; Czarnowicki, Tali ; Huynh, Thy ; Tran, Gary ; Lyon, Sarah ; Rodriguez, Giselle ; Immaneni, Supriya ; Johnson, Donald B. ; Bauer, Bruce ; Fuentes-Duculan, Judilyn ; Zheng, Xiuzhong ; Peng, Xiangyu ; Estrada, Yeriel D. ; Xu, Hui ; de Guzman Strong, Christina ; Suárez-Fariñas, Mayte ; Krueger, James G. ; Paller, Amy S. ; Guttman-Yassky, Emma. / Early-onset pediatric atopic dermatitis is TH2 but also TH17 polarized in skin. In: Journal of Allergy and Clinical Immunology. 2016 ; Vol. 138, No. 6. pp. 1639-1651.
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title = "Early-onset pediatric atopic dermatitis is TH2 but also TH17 polarized in skin",
abstract = "Background Atopic dermatitis (AD) affects 15{\%} to 25{\%} of children and 4{\%} to 7{\%} of adults. Paradigm-shifting discoveries about AD have been based on adult biomarkers, reflecting decades of disease activity, although 85{\%} of cases begin by 5 years. Blood phenotyping shows only TH2 skewing in patients with early-onset pediatric AD, but alterations in early pediatric skin lesions are unknown, limiting advancement of targeted therapies. Objective We sought to characterize the early pediatric AD skin phenotype and its differences from pediatric control subjects and adults with AD. Methods Using immunohistochemistry and quantitative real-time PCR, we assessed biopsy specimens from 19 children with AD younger than 5 years within 6 months of disease onset in comparison with adults with AD or psoriasis and pediatric and adult control subjects. Results In lesional skin children showed comparable or greater epidermal hyperplasia (thickness and keratin 16) and cellular infiltration (CD3+, CD11c+, and FcεRI+) than adults with AD. Similar to adults, strong activation of the TH2 (IL-13, IL-31, and CCL17) and TH22 (IL-22 and S100As) axes and some TH1 skewing (IFN-γ and CXCL10) were present. Children showed significantly higher induction of TH17-related cytokines and antimicrobials (IL-17A, IL-19, CCL20, LL37, and peptidase inhibitor 3/elafin), TH9/IL-9, IL-33, and innate markers (IL-8) than adults (P < .02). Despite the characteristic downregulation in adult patients with AD, filaggrin expression was similar in children with AD and healthy children. Nonlesional skin in pediatric patients with AD showed higher levels of inflammation (particularly IL-17A and the related molecules IL-19 and LL37) and epidermal proliferation (keratin 16 and S100As) markers (P < .001). Conclusion The skin phenotype of new-onset pediatric AD is substantially different from that of adult AD. Although excess TH2 activation characterizes both, TH9 and TH17 are highly activated at disease initiation. Increases in IL-19 levels might link TH2 and TH17 activation.",
author = "Hitokazu Esaki and Brunner, {Patrick M.} and Yael Renert-Yuval and Tali Czarnowicki and Thy Huynh and Gary Tran and Sarah Lyon and Giselle Rodriguez and Supriya Immaneni and Johnson, {Donald B.} and Bruce Bauer and Judilyn Fuentes-Duculan and Xiuzhong Zheng and Xiangyu Peng and Estrada, {Yeriel D.} and Hui Xu and {de Guzman Strong}, Christina and Mayte Su{\'a}rez-Fari{\~n}as and Krueger, {James G.} and Paller, {Amy S.} and Emma Guttman-Yassky",
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T1 - Early-onset pediatric atopic dermatitis is TH2 but also TH17 polarized in skin

AU - Esaki, Hitokazu

AU - Brunner, Patrick M.

AU - Renert-Yuval, Yael

AU - Czarnowicki, Tali

AU - Huynh, Thy

AU - Tran, Gary

AU - Lyon, Sarah

AU - Rodriguez, Giselle

AU - Immaneni, Supriya

AU - Johnson, Donald B.

AU - Bauer, Bruce

AU - Fuentes-Duculan, Judilyn

AU - Zheng, Xiuzhong

AU - Peng, Xiangyu

AU - Estrada, Yeriel D.

AU - Xu, Hui

AU - de Guzman Strong, Christina

AU - Suárez-Fariñas, Mayte

AU - Krueger, James G.

AU - Paller, Amy S.

AU - Guttman-Yassky, Emma

PY - 2016/12/1

Y1 - 2016/12/1

N2 - Background Atopic dermatitis (AD) affects 15% to 25% of children and 4% to 7% of adults. Paradigm-shifting discoveries about AD have been based on adult biomarkers, reflecting decades of disease activity, although 85% of cases begin by 5 years. Blood phenotyping shows only TH2 skewing in patients with early-onset pediatric AD, but alterations in early pediatric skin lesions are unknown, limiting advancement of targeted therapies. Objective We sought to characterize the early pediatric AD skin phenotype and its differences from pediatric control subjects and adults with AD. Methods Using immunohistochemistry and quantitative real-time PCR, we assessed biopsy specimens from 19 children with AD younger than 5 years within 6 months of disease onset in comparison with adults with AD or psoriasis and pediatric and adult control subjects. Results In lesional skin children showed comparable or greater epidermal hyperplasia (thickness and keratin 16) and cellular infiltration (CD3+, CD11c+, and FcεRI+) than adults with AD. Similar to adults, strong activation of the TH2 (IL-13, IL-31, and CCL17) and TH22 (IL-22 and S100As) axes and some TH1 skewing (IFN-γ and CXCL10) were present. Children showed significantly higher induction of TH17-related cytokines and antimicrobials (IL-17A, IL-19, CCL20, LL37, and peptidase inhibitor 3/elafin), TH9/IL-9, IL-33, and innate markers (IL-8) than adults (P < .02). Despite the characteristic downregulation in adult patients with AD, filaggrin expression was similar in children with AD and healthy children. Nonlesional skin in pediatric patients with AD showed higher levels of inflammation (particularly IL-17A and the related molecules IL-19 and LL37) and epidermal proliferation (keratin 16 and S100As) markers (P < .001). Conclusion The skin phenotype of new-onset pediatric AD is substantially different from that of adult AD. Although excess TH2 activation characterizes both, TH9 and TH17 are highly activated at disease initiation. Increases in IL-19 levels might link TH2 and TH17 activation.

AB - Background Atopic dermatitis (AD) affects 15% to 25% of children and 4% to 7% of adults. Paradigm-shifting discoveries about AD have been based on adult biomarkers, reflecting decades of disease activity, although 85% of cases begin by 5 years. Blood phenotyping shows only TH2 skewing in patients with early-onset pediatric AD, but alterations in early pediatric skin lesions are unknown, limiting advancement of targeted therapies. Objective We sought to characterize the early pediatric AD skin phenotype and its differences from pediatric control subjects and adults with AD. Methods Using immunohistochemistry and quantitative real-time PCR, we assessed biopsy specimens from 19 children with AD younger than 5 years within 6 months of disease onset in comparison with adults with AD or psoriasis and pediatric and adult control subjects. Results In lesional skin children showed comparable or greater epidermal hyperplasia (thickness and keratin 16) and cellular infiltration (CD3+, CD11c+, and FcεRI+) than adults with AD. Similar to adults, strong activation of the TH2 (IL-13, IL-31, and CCL17) and TH22 (IL-22 and S100As) axes and some TH1 skewing (IFN-γ and CXCL10) were present. Children showed significantly higher induction of TH17-related cytokines and antimicrobials (IL-17A, IL-19, CCL20, LL37, and peptidase inhibitor 3/elafin), TH9/IL-9, IL-33, and innate markers (IL-8) than adults (P < .02). Despite the characteristic downregulation in adult patients with AD, filaggrin expression was similar in children with AD and healthy children. Nonlesional skin in pediatric patients with AD showed higher levels of inflammation (particularly IL-17A and the related molecules IL-19 and LL37) and epidermal proliferation (keratin 16 and S100As) markers (P < .001). Conclusion The skin phenotype of new-onset pediatric AD is substantially different from that of adult AD. Although excess TH2 activation characterizes both, TH9 and TH17 are highly activated at disease initiation. Increases in IL-19 levels might link TH2 and TH17 activation.

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