CARD14 expression in dermal endothelial cells in psoriasis

Jamie L. Harden, Steven M. Lewis, Katherine C. Pierson, Mayte Suárez-Fariñas, Tim Lentini, Francesca S. Ortenzio, Lisa C. Zaba, Raphaela Goldbach-Mansky, Anne M. Bowcock, Michelle A. Lowes

Research output: Contribution to journalArticle

26 Citations (Scopus)

Abstract

Mutations in the caspase recruitment domain, family member 14 (CARD14) gene have recently been described in psoriasis patients, and explain the psoriasis susceptibility locus 2 (PSORS2). CARD14 is a scaffolding protein that regulates NF-κB activation, and psoriasis-associated CARD14 mutations lead to enhanced NF-κB signaling. CARD14 is expressed mainly in epidermal keratinocytes, but also in unidentified dermal cells. In this manuscript, the identity of the dermal cell types expressing CARD14, as well the potential functional consequence of overactive CARD14 in these dermal cell types, was determined. Using two-color immunofluorescence, dermal CARD14 did not co-localize with T-cells, dendritic cells, or macrophages. However, dermal CARD14 did highly co-localize with CD31(+) endothelial cells (ECs). CARD14 was also expressed non-dermal endothelial cells, such as aortic endothelial cells, which may indicate a role of CARD14(+)ECs in the systemic inflammation and cardiovascular comorbidities associated with psoriasis. Additionally, phosphorylated NF-κB was found in psoriatic CARD14(+) CD31(+) ECs, demonstrating this pathway is active in dermal ECs in psoriasis. Transfection of dermal ECs with psoriasis-associated CARD14 mutations resulted in increased expression of several chemokines, including CXCL10, IL-8, and CCL2. These results provide preliminary evidence that CARD14 expression in ECs may contribute to psoriasis through increased expression of chemokines and facilitating recruitment of immune cells into skin.

Original languageEnglish (US)
Pages (from-to)e111255
JournalPLoS One
Volume9
Issue number11
DOIs
StatePublished - 2014
Externally publishedYes

Fingerprint

psoriasis
caspases
Endothelial cells
Caspases
Psoriasis
endothelial cells
Endothelial Cells
Skin
Chemokines
Caspase Activation and Recruitment Domain
mutation
Mutation
Chemokine CXCL10
scaffolding proteins
cells
T-cells
Macrophages
keratinocytes
interleukin-8
Interleukin-8

ASJC Scopus subject areas

  • Medicine(all)

Cite this

Harden, J. L., Lewis, S. M., Pierson, K. C., Suárez-Fariñas, M., Lentini, T., Ortenzio, F. S., ... Lowes, M. A. (2014). CARD14 expression in dermal endothelial cells in psoriasis. PLoS One, 9(11), e111255. https://doi.org/10.1371/journal.pone.0111255

CARD14 expression in dermal endothelial cells in psoriasis. / Harden, Jamie L.; Lewis, Steven M.; Pierson, Katherine C.; Suárez-Fariñas, Mayte; Lentini, Tim; Ortenzio, Francesca S.; Zaba, Lisa C.; Goldbach-Mansky, Raphaela; Bowcock, Anne M.; Lowes, Michelle A.

In: PLoS One, Vol. 9, No. 11, 2014, p. e111255.

Research output: Contribution to journalArticle

Harden, JL, Lewis, SM, Pierson, KC, Suárez-Fariñas, M, Lentini, T, Ortenzio, FS, Zaba, LC, Goldbach-Mansky, R, Bowcock, AM & Lowes, MA 2014, 'CARD14 expression in dermal endothelial cells in psoriasis', PLoS One, vol. 9, no. 11, pp. e111255. https://doi.org/10.1371/journal.pone.0111255
Harden JL, Lewis SM, Pierson KC, Suárez-Fariñas M, Lentini T, Ortenzio FS et al. CARD14 expression in dermal endothelial cells in psoriasis. PLoS One. 2014;9(11):e111255. https://doi.org/10.1371/journal.pone.0111255
Harden, Jamie L. ; Lewis, Steven M. ; Pierson, Katherine C. ; Suárez-Fariñas, Mayte ; Lentini, Tim ; Ortenzio, Francesca S. ; Zaba, Lisa C. ; Goldbach-Mansky, Raphaela ; Bowcock, Anne M. ; Lowes, Michelle A. / CARD14 expression in dermal endothelial cells in psoriasis. In: PLoS One. 2014 ; Vol. 9, No. 11. pp. e111255.
@article{bf583e39014343fab50a132a91831c31,
title = "CARD14 expression in dermal endothelial cells in psoriasis",
abstract = "Mutations in the caspase recruitment domain, family member 14 (CARD14) gene have recently been described in psoriasis patients, and explain the psoriasis susceptibility locus 2 (PSORS2). CARD14 is a scaffolding protein that regulates NF-κB activation, and psoriasis-associated CARD14 mutations lead to enhanced NF-κB signaling. CARD14 is expressed mainly in epidermal keratinocytes, but also in unidentified dermal cells. In this manuscript, the identity of the dermal cell types expressing CARD14, as well the potential functional consequence of overactive CARD14 in these dermal cell types, was determined. Using two-color immunofluorescence, dermal CARD14 did not co-localize with T-cells, dendritic cells, or macrophages. However, dermal CARD14 did highly co-localize with CD31(+) endothelial cells (ECs). CARD14 was also expressed non-dermal endothelial cells, such as aortic endothelial cells, which may indicate a role of CARD14(+)ECs in the systemic inflammation and cardiovascular comorbidities associated with psoriasis. Additionally, phosphorylated NF-κB was found in psoriatic CARD14(+) CD31(+) ECs, demonstrating this pathway is active in dermal ECs in psoriasis. Transfection of dermal ECs with psoriasis-associated CARD14 mutations resulted in increased expression of several chemokines, including CXCL10, IL-8, and CCL2. These results provide preliminary evidence that CARD14 expression in ECs may contribute to psoriasis through increased expression of chemokines and facilitating recruitment of immune cells into skin.",
author = "Harden, {Jamie L.} and Lewis, {Steven M.} and Pierson, {Katherine C.} and Mayte Su{\'a}rez-Fari{\~n}as and Tim Lentini and Ortenzio, {Francesca S.} and Zaba, {Lisa C.} and Raphaela Goldbach-Mansky and Bowcock, {Anne M.} and Lowes, {Michelle A.}",
year = "2014",
doi = "10.1371/journal.pone.0111255",
language = "English (US)",
volume = "9",
pages = "e111255",
journal = "PLoS One",
issn = "1932-6203",
publisher = "Public Library of Science",
number = "11",

}

TY - JOUR

T1 - CARD14 expression in dermal endothelial cells in psoriasis

AU - Harden, Jamie L.

AU - Lewis, Steven M.

AU - Pierson, Katherine C.

AU - Suárez-Fariñas, Mayte

AU - Lentini, Tim

AU - Ortenzio, Francesca S.

AU - Zaba, Lisa C.

AU - Goldbach-Mansky, Raphaela

AU - Bowcock, Anne M.

AU - Lowes, Michelle A.

PY - 2014

Y1 - 2014

N2 - Mutations in the caspase recruitment domain, family member 14 (CARD14) gene have recently been described in psoriasis patients, and explain the psoriasis susceptibility locus 2 (PSORS2). CARD14 is a scaffolding protein that regulates NF-κB activation, and psoriasis-associated CARD14 mutations lead to enhanced NF-κB signaling. CARD14 is expressed mainly in epidermal keratinocytes, but also in unidentified dermal cells. In this manuscript, the identity of the dermal cell types expressing CARD14, as well the potential functional consequence of overactive CARD14 in these dermal cell types, was determined. Using two-color immunofluorescence, dermal CARD14 did not co-localize with T-cells, dendritic cells, or macrophages. However, dermal CARD14 did highly co-localize with CD31(+) endothelial cells (ECs). CARD14 was also expressed non-dermal endothelial cells, such as aortic endothelial cells, which may indicate a role of CARD14(+)ECs in the systemic inflammation and cardiovascular comorbidities associated with psoriasis. Additionally, phosphorylated NF-κB was found in psoriatic CARD14(+) CD31(+) ECs, demonstrating this pathway is active in dermal ECs in psoriasis. Transfection of dermal ECs with psoriasis-associated CARD14 mutations resulted in increased expression of several chemokines, including CXCL10, IL-8, and CCL2. These results provide preliminary evidence that CARD14 expression in ECs may contribute to psoriasis through increased expression of chemokines and facilitating recruitment of immune cells into skin.

AB - Mutations in the caspase recruitment domain, family member 14 (CARD14) gene have recently been described in psoriasis patients, and explain the psoriasis susceptibility locus 2 (PSORS2). CARD14 is a scaffolding protein that regulates NF-κB activation, and psoriasis-associated CARD14 mutations lead to enhanced NF-κB signaling. CARD14 is expressed mainly in epidermal keratinocytes, but also in unidentified dermal cells. In this manuscript, the identity of the dermal cell types expressing CARD14, as well the potential functional consequence of overactive CARD14 in these dermal cell types, was determined. Using two-color immunofluorescence, dermal CARD14 did not co-localize with T-cells, dendritic cells, or macrophages. However, dermal CARD14 did highly co-localize with CD31(+) endothelial cells (ECs). CARD14 was also expressed non-dermal endothelial cells, such as aortic endothelial cells, which may indicate a role of CARD14(+)ECs in the systemic inflammation and cardiovascular comorbidities associated with psoriasis. Additionally, phosphorylated NF-κB was found in psoriatic CARD14(+) CD31(+) ECs, demonstrating this pathway is active in dermal ECs in psoriasis. Transfection of dermal ECs with psoriasis-associated CARD14 mutations resulted in increased expression of several chemokines, including CXCL10, IL-8, and CCL2. These results provide preliminary evidence that CARD14 expression in ECs may contribute to psoriasis through increased expression of chemokines and facilitating recruitment of immune cells into skin.

UR - http://www.scopus.com/inward/record.url?scp=84934342782&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84934342782&partnerID=8YFLogxK

U2 - 10.1371/journal.pone.0111255

DO - 10.1371/journal.pone.0111255

M3 - Article

VL - 9

SP - e111255

JO - PLoS One

JF - PLoS One

SN - 1932-6203

IS - 11

ER -