An epidermotypic model of interface dermatitis reveals individual functions of fas ligand and gamma interferon in hypergranulosis, cytoid body formation, and gene expression

Sherry M. Farley, Lisa Wood, Mihail S. Iordanov

Research output: Contribution to journalArticle

2 Citations (Scopus)

Abstract

Analysis of complex cutaneous reactions using animal models allows for the identification of essential or modulatory participants, that is, cyto- and chemokines or adhesion molecules. However, complex whole animal modeling is bound to obscure some specific contributions of individual players. Mouse models suggest that expression of Fas ligand (FasL) by donor T cells is essential for the cutaneous acute graft-versus-host reaction (aGvHR), a major complication after allogeneic hematopoietic stem cell transplantation. The role of FasL/Fas in human cutaneous GvHR is not known. To understand the mechanisms of cytotoxicity and inflammation in human cutaneous GvHR, we developed an organotypic model using reconstructed human epidermis (RHE) that was exposed to FasL, gamma-interferon (IFNγ), or both. The model recapitulated key histological hallmarks of cutaneous aGvHR, including interface dermatitis, appearance of cytoid bodies, hypergranulosis, and expression of ICAM-1. Cytoid body formation and expression of ICAM-1 were attributable entirely to IFNγ, whereas hypergranulosis was triggered by FasL. Both FasL and IFNγ triggered vacuolar degeneration of keratinocytes. The validity of the RHE model of GvHR was demonstrated by histological correlation with biopsied skin from patients with acute graft-versus-host disease. FasL and IFNγ each elicited potent and specific proinflammatory genomic responses in RHE. Inhibition of caspase activity dramatically augmented the FasL-induced proinflammatory responses, suggesting an "apoptosis-versus- inflammation" antagonism in cutaneous aGvHR and other lichenoid dermatoses.

Original languageEnglish (US)
Pages (from-to)244-250
Number of pages7
JournalAmerican Journal of Dermatopathology
Volume33
Issue number3
DOIs
StatePublished - May 2011

Fingerprint

Fas Ligand Protein
Dermatitis
Interferon-gamma
Gene Expression
Skin
Epidermis
Interferons
Intercellular Adhesion Molecule-1
Transplants
Inflammation
Hematopoietic Stem Cell Transplantation
Graft vs Host Disease
Caspases
Keratinocytes
Chemokines
Skin Diseases
Animal Models
Tissue Donors
Apoptosis
Cytokines

Keywords

  • apoptosis
  • death ligand
  • death receptor
  • gene expression
  • inflammation

ASJC Scopus subject areas

  • Pathology and Forensic Medicine
  • Dermatology

Cite this

An epidermotypic model of interface dermatitis reveals individual functions of fas ligand and gamma interferon in hypergranulosis, cytoid body formation, and gene expression. / Farley, Sherry M.; Wood, Lisa; Iordanov, Mihail S.

In: American Journal of Dermatopathology, Vol. 33, No. 3, 05.2011, p. 244-250.

Research output: Contribution to journalArticle

@article{785f68e812404b0992defb512bc9cc9d,
title = "An epidermotypic model of interface dermatitis reveals individual functions of fas ligand and gamma interferon in hypergranulosis, cytoid body formation, and gene expression",
abstract = "Analysis of complex cutaneous reactions using animal models allows for the identification of essential or modulatory participants, that is, cyto- and chemokines or adhesion molecules. However, complex whole animal modeling is bound to obscure some specific contributions of individual players. Mouse models suggest that expression of Fas ligand (FasL) by donor T cells is essential for the cutaneous acute graft-versus-host reaction (aGvHR), a major complication after allogeneic hematopoietic stem cell transplantation. The role of FasL/Fas in human cutaneous GvHR is not known. To understand the mechanisms of cytotoxicity and inflammation in human cutaneous GvHR, we developed an organotypic model using reconstructed human epidermis (RHE) that was exposed to FasL, gamma-interferon (IFNγ), or both. The model recapitulated key histological hallmarks of cutaneous aGvHR, including interface dermatitis, appearance of cytoid bodies, hypergranulosis, and expression of ICAM-1. Cytoid body formation and expression of ICAM-1 were attributable entirely to IFNγ, whereas hypergranulosis was triggered by FasL. Both FasL and IFNγ triggered vacuolar degeneration of keratinocytes. The validity of the RHE model of GvHR was demonstrated by histological correlation with biopsied skin from patients with acute graft-versus-host disease. FasL and IFNγ each elicited potent and specific proinflammatory genomic responses in RHE. Inhibition of caspase activity dramatically augmented the FasL-induced proinflammatory responses, suggesting an {"}apoptosis-versus- inflammation{"} antagonism in cutaneous aGvHR and other lichenoid dermatoses.",
keywords = "apoptosis, death ligand, death receptor, gene expression, inflammation",
author = "Farley, {Sherry M.} and Lisa Wood and Iordanov, {Mihail S.}",
year = "2011",
month = "5",
doi = "10.1097/DAD.0b013e3181f1b200",
language = "English (US)",
volume = "33",
pages = "244--250",
journal = "American Journal of Dermatopathology",
issn = "0193-1091",
publisher = "Lippincott Williams and Wilkins",
number = "3",

}

TY - JOUR

T1 - An epidermotypic model of interface dermatitis reveals individual functions of fas ligand and gamma interferon in hypergranulosis, cytoid body formation, and gene expression

AU - Farley, Sherry M.

AU - Wood, Lisa

AU - Iordanov, Mihail S.

PY - 2011/5

Y1 - 2011/5

N2 - Analysis of complex cutaneous reactions using animal models allows for the identification of essential or modulatory participants, that is, cyto- and chemokines or adhesion molecules. However, complex whole animal modeling is bound to obscure some specific contributions of individual players. Mouse models suggest that expression of Fas ligand (FasL) by donor T cells is essential for the cutaneous acute graft-versus-host reaction (aGvHR), a major complication after allogeneic hematopoietic stem cell transplantation. The role of FasL/Fas in human cutaneous GvHR is not known. To understand the mechanisms of cytotoxicity and inflammation in human cutaneous GvHR, we developed an organotypic model using reconstructed human epidermis (RHE) that was exposed to FasL, gamma-interferon (IFNγ), or both. The model recapitulated key histological hallmarks of cutaneous aGvHR, including interface dermatitis, appearance of cytoid bodies, hypergranulosis, and expression of ICAM-1. Cytoid body formation and expression of ICAM-1 were attributable entirely to IFNγ, whereas hypergranulosis was triggered by FasL. Both FasL and IFNγ triggered vacuolar degeneration of keratinocytes. The validity of the RHE model of GvHR was demonstrated by histological correlation with biopsied skin from patients with acute graft-versus-host disease. FasL and IFNγ each elicited potent and specific proinflammatory genomic responses in RHE. Inhibition of caspase activity dramatically augmented the FasL-induced proinflammatory responses, suggesting an "apoptosis-versus- inflammation" antagonism in cutaneous aGvHR and other lichenoid dermatoses.

AB - Analysis of complex cutaneous reactions using animal models allows for the identification of essential or modulatory participants, that is, cyto- and chemokines or adhesion molecules. However, complex whole animal modeling is bound to obscure some specific contributions of individual players. Mouse models suggest that expression of Fas ligand (FasL) by donor T cells is essential for the cutaneous acute graft-versus-host reaction (aGvHR), a major complication after allogeneic hematopoietic stem cell transplantation. The role of FasL/Fas in human cutaneous GvHR is not known. To understand the mechanisms of cytotoxicity and inflammation in human cutaneous GvHR, we developed an organotypic model using reconstructed human epidermis (RHE) that was exposed to FasL, gamma-interferon (IFNγ), or both. The model recapitulated key histological hallmarks of cutaneous aGvHR, including interface dermatitis, appearance of cytoid bodies, hypergranulosis, and expression of ICAM-1. Cytoid body formation and expression of ICAM-1 were attributable entirely to IFNγ, whereas hypergranulosis was triggered by FasL. Both FasL and IFNγ triggered vacuolar degeneration of keratinocytes. The validity of the RHE model of GvHR was demonstrated by histological correlation with biopsied skin from patients with acute graft-versus-host disease. FasL and IFNγ each elicited potent and specific proinflammatory genomic responses in RHE. Inhibition of caspase activity dramatically augmented the FasL-induced proinflammatory responses, suggesting an "apoptosis-versus- inflammation" antagonism in cutaneous aGvHR and other lichenoid dermatoses.

KW - apoptosis

KW - death ligand

KW - death receptor

KW - gene expression

KW - inflammation

UR - http://www.scopus.com/inward/record.url?scp=79955523854&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=79955523854&partnerID=8YFLogxK

U2 - 10.1097/DAD.0b013e3181f1b200

DO - 10.1097/DAD.0b013e3181f1b200

M3 - Article

VL - 33

SP - 244

EP - 250

JO - American Journal of Dermatopathology

JF - American Journal of Dermatopathology

SN - 0193-1091

IS - 3

ER -