Amelioration of epidermal hyperplasia by TNF inhibition is associated with reduced Th17 responses.
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 beta-defensin 4). In contrast, Th1 cellular products and effector molecules (interferon gamma, lymphotoxin alpha, 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.
Zaba
Lisa C
LC
Laboratory for Investigative Dermatology, The Rockefeller University, New York, NY 10065, USA. lzaba@rockefeller.edu
Cardinale
Irma
I
Gilleaudeau
Patricia
P
Sullivan-Whalen
Mary
M
Suárez-Fariñas
Mayte
M
Suárez Fariñas
Mayte
M
Fuentes-Duculan
Judilyn
J
Novitskaya
Inna
I
Khatcherian
Artemis
A
Bluth
Mark J
MJ
Lowes
Michelle A
MA
Krueger
James G
JG
D003713:Dendritic Cells / Q000378:metabolism; D004817:Epidermis / Q000473:pathology*; D000068800:Etanercept; D006801:Humans; D006965:Hyperplasia / Q000378:metabolism*; D007074:Immunoglobulin G / Q000494:pharmacology; D007249:Inflammation; D020381:Interleukin-17 / Q000378:metabolism; D053759:Interleukin-23 / Q000378:metabolism; D019394:Ki-67 Antigen / Q000096:biosynthesis; D008264:Macrophages / Q000378:metabolism; D008954:Models, Biological; D022423:Myeloid Cells / Q000378:metabolism; D011565:Psoriasis / Q000378:metabolism; D018124:Receptors, Tumor Necrosis Factor; D006377:T-Lymphocytes, Helper-Inducer / Q000166:cytology*; D013997:Time Factors; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism*
D007074:Immunoglobulin G; D020381:Interleukin-17; D053759:Interleukin-23; D019394:Ki-67 Antigen; D018124:Receptors, Tumor Necrosis Factor; D014409:Tumor Necrosis Factor-alpha; D000068800:Etanercept