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¹ Laboratory for Investigative Dermatology, The Rockefeller University, New York, NY 10065
² Department of Dermatology, Weill Medical College of Cornell University, New York, NY 10065

CORRESPONDENCE Lisa C. Zaba: lzaba{at}rockefeller.edu

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 , lymphotoxin , 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.

Abbreviations used: CCL, CC chemokine ligand; DC-LAMP, DC–lysosomal-associated membrane protein; DEFB4, β-defensin 4; EAE, experimental autoimmune encephalomyelitis; HARP, human acidic ribosomal protein; IBD, inflammatory bowel disease; ICAM, intracellular adhesion molecule; iNOS, inducible NO synthase; K16, keratin 16; LTA, lymphotoxin ; MFI, mean fluorescence intensity; MLR, mixed leukocyte reaction; MoDC, monocyte-derived DC; mRNA, messenger RNA; MX-1, myxovirus resistance 1; PASI, psoriasis area and severity index; TipDC, TNF–iNOS-producing DC.

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