TY - JOUR
T1 - Amelioration of epidermal hyperplasia by TNF inhibition is associated with reduced Th17 responses
AU - Zaba, Lisa C.
AU - Cardinale, Irma
AU - Gilleaudeau, Patricia
AU - Sullivan-Whalen, Mary
AU - Fariñas, Mayte Suárez
AU - Fuentes-Duculan, Judilyn
AU - Novitskaya, Inna
AU - Khatcherian, Artemis
AU - Bluth, Mark J.
AU - Lowes, Michelle A.
AU - Krueger, James G.
PY - 2007/12/24
Y1 - 2007/12/24
N2 - Biological agents have dramatically improved treatment options for patients with severe psoriasis. Etanercept (tumor necrosis factor [TNF] receptor-immunoglobulin fusion protein) is an effective treatment for many psoriasis patients, and blockade of TNF is considered to be its primary action. However, in this clinical trial, we show that etanercept has early inhibitory effects on a newly appreciated type of T cells: T helper type 17 (Th17) cells. Etanercept reduced the inflammatory dendritic cell products that drive Th17 cell proliferation (interleukin [IL] 23), as well as Th17 cell products and downstream effector molecules (IL-17, IL-22, CC chemokine ligand 20, and β-defensin 4). In contrast, Th1 cellular products and effector molecules (interferon γ, lymphotoxin α, and myxovirus resistance 1) were reduced late in disease resolution. This study suggests a role for Th17 in addition to Th1 cells in the pathogenesis of psoriasis. Th17 cells may be particularly important in driving epidermal activation in psoriatic plaques, whereas Th1 cells must also be eliminated for final disease resolution. JEM
AB - Biological agents have dramatically improved treatment options for patients with severe psoriasis. Etanercept (tumor necrosis factor [TNF] receptor-immunoglobulin fusion protein) is an effective treatment for many psoriasis patients, and blockade of TNF is considered to be its primary action. However, in this clinical trial, we show that etanercept has early inhibitory effects on a newly appreciated type of T cells: T helper type 17 (Th17) cells. Etanercept reduced the inflammatory dendritic cell products that drive Th17 cell proliferation (interleukin [IL] 23), as well as Th17 cell products and downstream effector molecules (IL-17, IL-22, CC chemokine ligand 20, and β-defensin 4). In contrast, Th1 cellular products and effector molecules (interferon γ, lymphotoxin α, and myxovirus resistance 1) were reduced late in disease resolution. This study suggests a role for Th17 in addition to Th1 cells in the pathogenesis of psoriasis. Th17 cells may be particularly important in driving epidermal activation in psoriatic plaques, whereas Th1 cells must also be eliminated for final disease resolution. JEM
UR - http://www.scopus.com/inward/record.url?scp=37549011317&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=37549011317&partnerID=8YFLogxK
U2 - 10.1084/jem.20071094
DO - 10.1084/jem.20071094
M3 - Article
C2 - 18039949
AN - SCOPUS:37549011317
SN - 0022-1007
VL - 204
SP - 3183
EP - 3194
JO - Journal of Experimental Medicine
JF - Journal of Experimental Medicine
IS - 13
ER -