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. Paller; Emma Guttman-Yassky

doi:10.1016/j.jaci.2016.07.013

Early-onset pediatric atopic dermatitis is T_H2 but also T_H17 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^*

^*Corresponding author for this work

Research output: Contribution to journal › Article › peer-review

320 Scopus citations

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 T_H2 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 T_H2 (IL-13, IL-31, and CCL17) and T_H22 (IL-22 and S100As) axes and some T_H1 skewing (IFN-γ and CXCL10) were present. Children showed significantly higher induction of T_H17-related cytokines and antimicrobials (IL-17A, IL-19, CCL20, LL37, and peptidase inhibitor 3/elafin), T_H9/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 T_H2 activation characterizes both, T_H9 and T_H17 are highly activated at disease initiation. Increases in IL-19 levels might link T_H2 and T_H17 activation.

Original language	English (US)
Pages (from-to)	1639-1651
Number of pages	13
Journal	Journal of Allergy and Clinical Immunology
Volume	138
Issue number	6
DOIs	https://doi.org/10.1016/j.jaci.2016.07.013
State	Published - Dec 1 2016

Funding

Supported by a research grant from the LEO Foundation . P.M.B. and M.S.-F. were supported in part by grant no. UL1 TR00043 from the National Center for Advancing Translational Sciences (NCATS), National Institutes of Health (NIH) Clinical and Translational Science Award (CTSA) program.

Keywords

Atopic dermatitis
IL-17
IL-19
T17
T2
T9
adult
antimicrobials
pediatric
skin

ASJC Scopus subject areas

Immunology and Allergy
Immunology

Access to Document

10.1016/j.jaci.2016.07.013

Cite this

Esaki, H., Brunner, P. M., Renert-Yuval, Y., Czarnowicki, T., Huynh, T., Tran, G., Lyon, S., Rodriguez, G., Immaneni, S., Johnson, D. B., Bauer, B., Fuentes-Duculan, J., Zheng, X., Peng, X., Estrada, Y. D., Xu, H., de Guzman Strong, C., Suárez-Fariñas, M., Krueger, J. G., ... Guttman-Yassky, E. (2016). Early-onset pediatric atopic dermatitis is T_H2 but also T_H17 polarized in skin. Journal of Allergy and Clinical Immunology, 138(6), 1639-1651. https://doi.org/10.1016/j.jaci.2016.07.013

@article{1e4bfdd9bba14c45a87bff70c3fecd8c,

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.",

keywords = "Atopic dermatitis, IL-17, IL-19, T17, T2, T9, adult, antimicrobials, pediatric, skin",

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",

note = "Publisher Copyright: {\textcopyright} 2016 American Academy of Allergy, Asthma & Immunology",

year = "2016",

month = dec,

day = "1",

doi = "10.1016/j.jaci.2016.07.013",

language = "English (US)",

volume = "138",

pages = "1639--1651",

journal = "Journal of Allergy and Clinical Immunology",

issn = "0091-6749",

publisher = "Mosby Inc.",

number = "6",

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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 T_H2 but also T_H17 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

TY - JOUR

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.

KW - Atopic dermatitis

KW - IL-17

KW - IL-19

KW - T17

KW - T2

KW - T9

KW - adult

KW - antimicrobials

KW - pediatric

KW - skin

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DO - 10.1016/j.jaci.2016.07.013

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