title: TREM-1 as a potential therapeutic target in psoriasis.
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.
authors: Laboratory for Investigative Dermatology, The Rockefeller University, New York, New York 10065, USA.
authors: Luke A
authors: LA
authors: Hyder
authors: Juana
authors: J
authors: Gonzalez
authors: Jamie L
authors: JL
authors: Harden
authors: Leanne M
authors: LM
authors: Johnson-Huang
authors: Lisa C
authors: LC
authors: Zaba
authors: Katherine C
authors: KC
authors: Pierson
authors: Narat J
authors: NJ
authors: Eungdamrong
authors: Tim
authors: T
authors: Lentini
authors: Nicholas
authors: N
authors: Gulati
authors: Judilyn
authors: J
authors: Fuentes-Duculan
authors: Mayte
authors: M
authors: Suárez-Fariñas
authors: Michelle A
authors: MA
authors: Lowes
mesh_terms: D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000627:therapeutic use; D039521:CD11c Antigen / Q000378:metabolism; D002478:Cells, Cultured; D016207:Cytokines / Q000378:metabolism; D000068800:Etanercept; D005260:Female; D006801:Humans; D007074:Immunoglobulin G / Q000627:therapeutic use; D066298:In Vitro Techniques; D020381:Interleukin-17 / Q000378:metabolism; D007801:Langerhans Cells / Q000276:immunology / Q000378:metabolism* / Q000473:pathology; D008297:Male; D008562:Membrane Glycoproteins / Q000037:antagonists & inhibitors* / Q000378:metabolism*; D008875:Middle Aged; D009000:Monocytes / Q000378:metabolism / Q000473:pathology; D011565:Psoriasis / Q000378:metabolism* / Q000473:pathology / Q000628:therapy*; D011971:Receptors, Immunologic / Q000037:antagonists & inhibitors* / Q000378:metabolism*; D018124:Receptors, Tumor Necrosis Factor / Q000627:therapeutic use; D015398:Signal Transduction / Q000502:physiology*; D058504:Th17 Cells / Q000378:metabolism / Q000473:pathology; D000073871:Triggering Receptor Expressed on Myeloid Cells-1; D014467:Ultraviolet Therapy
chemical_list: D000894:Anti-Inflammatory Agents, Non-Steroidal; D039521:CD11c Antigen; D016207:Cytokines; D007074:Immunoglobulin G; D020381:Interleukin-17; D008562:Membrane Glycoproteins; D011971:Receptors, Immunologic; D018124:Receptors, Tumor Necrosis Factor; C408842:TREM1 protein, human; D000073871:Triggering Receptor Expressed on Myeloid Cells-1; D000068800:Etanercept