TREM-1 as a potential therapeutic target in psoriasis

Luke A. Hyder, Juana Gonzalez, Jamie L. Harden, Leanne M. Johnson-Huang, Lisa C. Zaba, Katherine C. Pierson, Narat J. Eungdamrong, Tim Lentini, Nicholas Gulati, Judilyn Fuentes-Duculan, Mayte Suárez-Fariñas, Michelle A. Lowes

Research output: Contribution to journalArticle

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Abstract

Our group recently described a population of antigen-presenting cells that appear to be critical in psoriasis pathogenesis, termed inflammatory myeloid dendritic cells (CD11c + /blood dendritic cell (DC) antigen 1 -). Triggering receptor expressed on myeloid cells type-1 (TREM-1) signaling was a major canonical pathway in the published transcriptome of these cells. TREM-1 is a member of the Ig superfamily, active through the DAP12 signaling pathway, with an unknown ligand. Activation through TREM-1 induces inflammatory cytokines, including IL-8, MCP/CCL2, and tumor necrosis factor. We now show that TREM-1 was expressed in the skin of healthy and psoriatic patients, and there was increased soluble TREM-1 in the circulation of psoriasis patients. In psoriasis lesions, TREM-1 was colocalized with DCs, as well as CD31 + endothelial cells. TREM-1 expression was reduced with successful narrow band UVB (NB-UVB), etanercept, and anti-IL-17 treatments. An in vitro model of peptidoglycan- activated monocytes as inflammatory myeloid DCs was developed to study TREM-1 blockade, and treatment with a TREM-1 blocking chimera decreased allogeneic T-helper type 17 cell activation, as well as IL-17 production. Furthermore, TREM-1 blockade of ex vivo psoriatic DCs in an allogeneic mixed leukocyte reaction also showed a decrease in IL-17. Together, these data suggest that the TREM-1 signaling pathway may be a previously unidentified therapeutic target to prevent the effects of inflammatory myeloid DCs in psoriasis.

Original languageEnglish (US)
Pages (from-to)1742-1751
Number of pages10
JournalJournal of Investigative Dermatology
Volume133
Issue number7
DOIs
StatePublished - Jul 2013
Externally publishedYes

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Interleukin-17
Myeloid Cells
Psoriasis
Chemical activation
Peptidoglycan
Endothelial cells
Interleukin-8
Skin
Blood
Therapeutics
Tumor Necrosis Factor-alpha
Cytokines
Ligands
Antigens
Dendritic Cells
Th17 Cells
Mixed Lymphocyte Culture Test
Antigen-Presenting Cells
Transcriptome
Monocytes

ASJC Scopus subject areas

  • Dermatology
  • Biochemistry
  • Cell Biology
  • Molecular Biology

Cite this

Hyder, L. A., Gonzalez, J., Harden, J. L., Johnson-Huang, L. M., Zaba, L. C., Pierson, K. C., ... Lowes, M. A. (2013). TREM-1 as a potential therapeutic target in psoriasis. Journal of Investigative Dermatology, 133(7), 1742-1751. https://doi.org/10.1038/jid.2013.68

TREM-1 as a potential therapeutic target in psoriasis. / Hyder, Luke A.; Gonzalez, Juana; Harden, Jamie L.; Johnson-Huang, Leanne M.; Zaba, Lisa C.; Pierson, Katherine C.; Eungdamrong, Narat J.; Lentini, Tim; Gulati, Nicholas; Fuentes-Duculan, Judilyn; Suárez-Fariñas, Mayte; Lowes, Michelle A.

In: Journal of Investigative Dermatology, Vol. 133, No. 7, 07.2013, p. 1742-1751.

Research output: Contribution to journalArticle

Hyder, LA, Gonzalez, J, Harden, JL, Johnson-Huang, LM, Zaba, LC, Pierson, KC, Eungdamrong, NJ, Lentini, T, Gulati, N, Fuentes-Duculan, J, Suárez-Fariñas, M & Lowes, MA 2013, 'TREM-1 as a potential therapeutic target in psoriasis', Journal of Investigative Dermatology, vol. 133, no. 7, pp. 1742-1751. https://doi.org/10.1038/jid.2013.68
Hyder LA, Gonzalez J, Harden JL, Johnson-Huang LM, Zaba LC, Pierson KC et al. TREM-1 as a potential therapeutic target in psoriasis. Journal of Investigative Dermatology. 2013 Jul;133(7):1742-1751. https://doi.org/10.1038/jid.2013.68
Hyder, Luke A. ; Gonzalez, Juana ; Harden, Jamie L. ; Johnson-Huang, Leanne M. ; Zaba, Lisa C. ; Pierson, Katherine C. ; Eungdamrong, Narat J. ; Lentini, Tim ; Gulati, Nicholas ; Fuentes-Duculan, Judilyn ; Suárez-Fariñas, Mayte ; Lowes, Michelle A. / TREM-1 as a potential therapeutic target in psoriasis. In: Journal of Investigative Dermatology. 2013 ; Vol. 133, No. 7. pp. 1742-1751.
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