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.
authors.affiliation: Laboratory for Investigative Dermatology, The Rockefeller University, New York, New York, United States of America.
authors.forename: Jamie L
authors.initials: JL
authors.lastname: Harden
authors.affiliation: Laboratory for Investigative Dermatology, The Rockefeller University, New York, New York, United States of America.
authors.forename: Steven M
authors.initials: SM
authors.lastname: Lewis
authors.affiliation: Laboratory for Investigative Dermatology, The Rockefeller University, New York, New York, United States of America.
authors.forename: Katherine C
authors.initials: KC
authors.lastname: Pierson
authors.affiliation: Laboratory for Investigative Dermatology, The Rockefeller University, New York, New York, United States of America; Center for Clinical and Translational Science, The Rockefeller University, New York, New York, United States of America.
authors.forename: Mayte
authors.initials: M
authors.lastname: Suárez-Fariñas
authors.affiliation: Laboratory for Investigative Dermatology, The Rockefeller University, New York, New York, United States of America.
authors.forename: Tim
authors.initials: T
authors.lastname: Lentini
authors.affiliation: Laboratory for Investigative Dermatology, The Rockefeller University, New York, New York, United States of America.
authors.forename: Francesca S
authors.initials: FS
authors.lastname: Ortenzio
authors.affiliation: Laboratory for Investigative Dermatology, The Rockefeller University, New York, New York, United States of America.
authors.forename: Lisa C
authors.initials: LC
authors.lastname: Zaba
authors.affiliation: Translational Autoinflammatory Disease Section NIAMS/NIH, Bethesda, MD, United States of America.
authors.forename: Raphaela
authors.initials: R
authors.lastname: Goldbach-Mansky
authors.affiliation: Genomic Medicine, Imperial College London, London, England.
authors.forename: Anne M
authors.initials: AM
authors.lastname: Bowcock
authors.affiliation: Laboratory for Investigative Dermatology, The Rockefeller University, New York, New York, United States of America.
authors.forename: Michelle A
authors.initials: MA
authors.lastname: Lowes
mesh_terms: D053468:CARD Signaling Adaptor Proteins / Q000235:genetics / Q000378:metabolism*; D002478:Cells, Cultured; D018932:Chemokine CCL2 / Q000378:metabolism; D054357:Chemokine CXCL10 / Q000378:metabolism; D020405:Dermis / Q000166:cytology; D042783:Endothelial Cells / Q000166:cytology / Q000378:metabolism*; D006162:Guanylate Cyclase / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D016209:Interleukin-8 / Q000378:metabolism; D015603:Keratinocytes / Q000378:metabolism; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism*; D009000:Monocytes / Q000276:immunology / Q000378:metabolism; D009154:Mutation; D016328:NF-kappa B / Q000378:metabolism; D010766:Phosphorylation; D019408:Platelet Endothelial Cell Adhesion Molecule-1 / Q000378:metabolism; D011565:Psoriasis / Q000378:metabolism / Q000473:pathology*; D012333:RNA, Messenger / Q000378:metabolism; D015398:Signal Transduction; D013601:T-Lymphocytes / Q000276:immunology / Q000378:metabolism; D059467:Transcriptome; D014162:Transfection
chemical_list: D053468:CARD Signaling Adaptor Proteins; D018932:Chemokine CCL2; D054357:Chemokine CXCL10; D016209:Interleukin-8; D008565:Membrane Proteins; D016328:NF-kappa B; D019408:Platelet Endothelial Cell Adhesion Molecule-1; D012333:RNA, Messenger; C426243:CARD14 protein, human; D006162:Guanylate Cyclase