TY - JOUR
T1 - TREM-1 as a potential therapeutic target in psoriasis
AU - Hyder, Luke A.
AU - Gonzalez, Juana
AU - Harden, Jamie L.
AU - Johnson-Huang, Leanne M.
AU - Zaba, Lisa C.
AU - Pierson, Katherine C.
AU - Eungdamrong, Narat J.
AU - Lentini, Tim
AU - Gulati, Nicholas
AU - Fuentes-Duculan, Judilyn
AU - Suárez-Fariñas, Mayte
AU - Lowes, Michelle A.
N1 - Funding Information:
This research was supported by National Institutes of Health (NIH) grant UL1 RR024143 from the National Center for Research Resources (NCRR). MAL, LH, and JLH are supported by NIH 1R01AR060222; LMJ-H is supported by the Linda and Leonard Berkowitz Postdoctoral Fellowship. NG is supported by NIH MSTP grant GM07739. TL is supported by a National Psoriasis Foundation Discovery grant. We would like to thank Dr James Krueger for helpful discussions, Hanna Ning and Dr Hiroshi Mitsui for technical advice, and Drs Shivaprasad Bhuvanendran and Alison North from the Bio-Imaging Resource Center for technical support. We greatly appreciate Patricia Gilleadeau and Mary Sullivan-Whalen for excellent care of our patients.
PY - 2013/7
Y1 - 2013/7
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=84879419176&partnerID=8YFLogxK
U2 - 10.1038/jid.2013.68
DO - 10.1038/jid.2013.68
M3 - Article
AN - SCOPUS:84879419176
SN - 0022-202X
VL - 133
SP - 1742
EP - 1751
JO - Journal of Investigative Dermatology
JF - Journal of Investigative Dermatology
IS - 7
ER -