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

33 Scopus citations

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

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Dermatology
  • Cell Biology

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    Hyder, L. A., Gonzalez, J., Harden, J. L., Johnson-Huang, L. M., Zaba, L. C., Pierson, K. C., Eungdamrong, N. J., Lentini, T., Gulati, N., Fuentes-Duculan, J., Suárez-Fariñas, M., & 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