Th17 cytokines interleukin (IL)-17 and IL-22 modulate distinct inflammatory and keratinocyte-response pathways

K. E. Nograles, L. C. Zaba, E. Guttman-Yassky, J. Fuentes-Duculan, M. Suárez-Fariñas, I. Cardinale, A. Khatcherian, J. Gonzalez, K. C. Pierson, T. R. White, C. Pensabene, I. Coats, I. Novitskaya, M. A. Lowes, J. G. Krueger

Research output: Contribution to journalArticle

505 Citations (Scopus)

Abstract

Background: Psoriasis vulgaris is an inflammatory skin disease mediated by Th1 and Th17 cytokines, yet the relative contribution of interferon (IFN)-γ, interleukin (IL)-17 and IL-22 on disease pathogenesis is still unknown. Objectives: In this study, we sought to identify the cytokines produced by skin-resident T cells in normal skin, localize the receptors for these cytokines, and examine how these cytokines alter gene expression profiles of the cells bearing cognate receptors. Methods: We used intracellular cytokine staining and flow cytometry to evaluate T cell cytokine production, and immunohistochemistry and double-label immunofluorescence to localize cytokine receptors in skin. Gene array analysis of cytokine-treated keratinocytes was performed using moderated paired t-test controlling for false discovery rate using the Benjamini-Hochberg procedure. Results: We demonstrate that T-helper cells producing IL-17, IL-22 and/or IFN-γ, as well as the cells bearing cognate cytokine receptors, are present in normal human skin. Keratinocytes stimulated with IL-17 expressed chemokines that were different from those induced by IFN-γ, probably contributing to the influx of neutrophils, dendritic cells and memory T cells into the psoriatic lesion. In contrast, IL-22 downregulated genes associated with keratinocyte differentiation and caused epidermal alterations in an organotypic skin model. Conclusions: Our results suggest that the Th17 cytokines IL-17 and IL-22 mediate distinct downstream pathways that contribute to the psoriatic phenotype: IL-17 is more proinflammatory, while IL-22 retards keratinocyte differentiation.

Original languageEnglish (US)
Pages (from-to)1092-1102
Number of pages11
JournalBritish Journal of Dermatology
Volume159
Issue number5
DOIs
StatePublished - Nov 2008
Externally publishedYes

Fingerprint

Interleukin-17
Keratinocytes
Cytokines
Cytokine Receptors
Skin
Interferons
T-Lymphocytes
Helper-Inducer T-Lymphocytes
interleukin-22
Transcriptome
Chemokines
Psoriasis
Skin Diseases
Dendritic Cells
Genes
Fluorescent Antibody Technique
Flow Cytometry
Neutrophils
Down-Regulation
Immunohistochemistry

Keywords

  • Interleukin-17
  • Interleukin-22
  • Keratinocytes
  • Th1
  • Th17

ASJC Scopus subject areas

  • Dermatology

Cite this

Nograles, K. E., Zaba, L. C., Guttman-Yassky, E., Fuentes-Duculan, J., Suárez-Fariñas, M., Cardinale, I., ... Krueger, J. G. (2008). Th17 cytokines interleukin (IL)-17 and IL-22 modulate distinct inflammatory and keratinocyte-response pathways. British Journal of Dermatology, 159(5), 1092-1102. https://doi.org/10.1111/j.1365-2133.2008.08769.x

Th17 cytokines interleukin (IL)-17 and IL-22 modulate distinct inflammatory and keratinocyte-response pathways. / Nograles, K. E.; Zaba, L. C.; Guttman-Yassky, E.; Fuentes-Duculan, J.; Suárez-Fariñas, M.; Cardinale, I.; Khatcherian, A.; Gonzalez, J.; Pierson, K. C.; White, T. R.; Pensabene, C.; Coats, I.; Novitskaya, I.; Lowes, M. A.; Krueger, J. G.

In: British Journal of Dermatology, Vol. 159, No. 5, 11.2008, p. 1092-1102.

Research output: Contribution to journalArticle

Nograles, KE, Zaba, LC, Guttman-Yassky, E, Fuentes-Duculan, J, Suárez-Fariñas, M, Cardinale, I, Khatcherian, A, Gonzalez, J, Pierson, KC, White, TR, Pensabene, C, Coats, I, Novitskaya, I, Lowes, MA & Krueger, JG 2008, 'Th17 cytokines interleukin (IL)-17 and IL-22 modulate distinct inflammatory and keratinocyte-response pathways', British Journal of Dermatology, vol. 159, no. 5, pp. 1092-1102. https://doi.org/10.1111/j.1365-2133.2008.08769.x
Nograles KE, Zaba LC, Guttman-Yassky E, Fuentes-Duculan J, Suárez-Fariñas M, Cardinale I et al. Th17 cytokines interleukin (IL)-17 and IL-22 modulate distinct inflammatory and keratinocyte-response pathways. British Journal of Dermatology. 2008 Nov;159(5):1092-1102. https://doi.org/10.1111/j.1365-2133.2008.08769.x
Nograles, K. E. ; Zaba, L. C. ; Guttman-Yassky, E. ; Fuentes-Duculan, J. ; Suárez-Fariñas, M. ; Cardinale, I. ; Khatcherian, A. ; Gonzalez, J. ; Pierson, K. C. ; White, T. R. ; Pensabene, C. ; Coats, I. ; Novitskaya, I. ; Lowes, M. A. ; Krueger, J. G. / Th17 cytokines interleukin (IL)-17 and IL-22 modulate distinct inflammatory and keratinocyte-response pathways. In: British Journal of Dermatology. 2008 ; Vol. 159, No. 5. pp. 1092-1102.
@article{017848953d00414c8864559366f5d94f,
title = "Th17 cytokines interleukin (IL)-17 and IL-22 modulate distinct inflammatory and keratinocyte-response pathways",
abstract = "Background: Psoriasis vulgaris is an inflammatory skin disease mediated by Th1 and Th17 cytokines, yet the relative contribution of interferon (IFN)-γ, interleukin (IL)-17 and IL-22 on disease pathogenesis is still unknown. Objectives: In this study, we sought to identify the cytokines produced by skin-resident T cells in normal skin, localize the receptors for these cytokines, and examine how these cytokines alter gene expression profiles of the cells bearing cognate receptors. Methods: We used intracellular cytokine staining and flow cytometry to evaluate T cell cytokine production, and immunohistochemistry and double-label immunofluorescence to localize cytokine receptors in skin. Gene array analysis of cytokine-treated keratinocytes was performed using moderated paired t-test controlling for false discovery rate using the Benjamini-Hochberg procedure. Results: We demonstrate that T-helper cells producing IL-17, IL-22 and/or IFN-γ, as well as the cells bearing cognate cytokine receptors, are present in normal human skin. Keratinocytes stimulated with IL-17 expressed chemokines that were different from those induced by IFN-γ, probably contributing to the influx of neutrophils, dendritic cells and memory T cells into the psoriatic lesion. In contrast, IL-22 downregulated genes associated with keratinocyte differentiation and caused epidermal alterations in an organotypic skin model. Conclusions: Our results suggest that the Th17 cytokines IL-17 and IL-22 mediate distinct downstream pathways that contribute to the psoriatic phenotype: IL-17 is more proinflammatory, while IL-22 retards keratinocyte differentiation.",
keywords = "Interleukin-17, Interleukin-22, Keratinocytes, Th1, Th17",
author = "Nograles, {K. E.} and Zaba, {L. C.} and E. Guttman-Yassky and J. Fuentes-Duculan and M. Su{\'a}rez-Fari{\~n}as and I. Cardinale and A. Khatcherian and J. Gonzalez and Pierson, {K. C.} and White, {T. R.} and C. Pensabene and I. Coats and I. Novitskaya and Lowes, {M. A.} and Krueger, {J. G.}",
year = "2008",
month = "11",
doi = "10.1111/j.1365-2133.2008.08769.x",
language = "English (US)",
volume = "159",
pages = "1092--1102",
journal = "British Journal of Dermatology",
issn = "0007-0963",
publisher = "Wiley-Blackwell",
number = "5",

}

TY - JOUR

T1 - Th17 cytokines interleukin (IL)-17 and IL-22 modulate distinct inflammatory and keratinocyte-response pathways

AU - Nograles, K. E.

AU - Zaba, L. C.

AU - Guttman-Yassky, E.

AU - Fuentes-Duculan, J.

AU - Suárez-Fariñas, M.

AU - Cardinale, I.

AU - Khatcherian, A.

AU - Gonzalez, J.

AU - Pierson, K. C.

AU - White, T. R.

AU - Pensabene, C.

AU - Coats, I.

AU - Novitskaya, I.

AU - Lowes, M. A.

AU - Krueger, J. G.

PY - 2008/11

Y1 - 2008/11

N2 - Background: Psoriasis vulgaris is an inflammatory skin disease mediated by Th1 and Th17 cytokines, yet the relative contribution of interferon (IFN)-γ, interleukin (IL)-17 and IL-22 on disease pathogenesis is still unknown. Objectives: In this study, we sought to identify the cytokines produced by skin-resident T cells in normal skin, localize the receptors for these cytokines, and examine how these cytokines alter gene expression profiles of the cells bearing cognate receptors. Methods: We used intracellular cytokine staining and flow cytometry to evaluate T cell cytokine production, and immunohistochemistry and double-label immunofluorescence to localize cytokine receptors in skin. Gene array analysis of cytokine-treated keratinocytes was performed using moderated paired t-test controlling for false discovery rate using the Benjamini-Hochberg procedure. Results: We demonstrate that T-helper cells producing IL-17, IL-22 and/or IFN-γ, as well as the cells bearing cognate cytokine receptors, are present in normal human skin. Keratinocytes stimulated with IL-17 expressed chemokines that were different from those induced by IFN-γ, probably contributing to the influx of neutrophils, dendritic cells and memory T cells into the psoriatic lesion. In contrast, IL-22 downregulated genes associated with keratinocyte differentiation and caused epidermal alterations in an organotypic skin model. Conclusions: Our results suggest that the Th17 cytokines IL-17 and IL-22 mediate distinct downstream pathways that contribute to the psoriatic phenotype: IL-17 is more proinflammatory, while IL-22 retards keratinocyte differentiation.

AB - Background: Psoriasis vulgaris is an inflammatory skin disease mediated by Th1 and Th17 cytokines, yet the relative contribution of interferon (IFN)-γ, interleukin (IL)-17 and IL-22 on disease pathogenesis is still unknown. Objectives: In this study, we sought to identify the cytokines produced by skin-resident T cells in normal skin, localize the receptors for these cytokines, and examine how these cytokines alter gene expression profiles of the cells bearing cognate receptors. Methods: We used intracellular cytokine staining and flow cytometry to evaluate T cell cytokine production, and immunohistochemistry and double-label immunofluorescence to localize cytokine receptors in skin. Gene array analysis of cytokine-treated keratinocytes was performed using moderated paired t-test controlling for false discovery rate using the Benjamini-Hochberg procedure. Results: We demonstrate that T-helper cells producing IL-17, IL-22 and/or IFN-γ, as well as the cells bearing cognate cytokine receptors, are present in normal human skin. Keratinocytes stimulated with IL-17 expressed chemokines that were different from those induced by IFN-γ, probably contributing to the influx of neutrophils, dendritic cells and memory T cells into the psoriatic lesion. In contrast, IL-22 downregulated genes associated with keratinocyte differentiation and caused epidermal alterations in an organotypic skin model. Conclusions: Our results suggest that the Th17 cytokines IL-17 and IL-22 mediate distinct downstream pathways that contribute to the psoriatic phenotype: IL-17 is more proinflammatory, while IL-22 retards keratinocyte differentiation.

KW - Interleukin-17

KW - Interleukin-22

KW - Keratinocytes

KW - Th1

KW - Th17

UR - http://www.scopus.com/inward/record.url?scp=54249130813&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=54249130813&partnerID=8YFLogxK

U2 - 10.1111/j.1365-2133.2008.08769.x

DO - 10.1111/j.1365-2133.2008.08769.x

M3 - Article

C2 - 18684158

AN - SCOPUS:54249130813

VL - 159

SP - 1092

EP - 1102

JO - British Journal of Dermatology

JF - British Journal of Dermatology

SN - 0007-0963

IS - 5

ER -