Amelioration of epidermal hyperplasia by TNF inhibition is associated with reduced Th17 responses

By Lisa C. Zaba, I. Cardinale, P. Gilleaudeau, M. Sullivan-Whalen, M. Suárez‐Fariñas, J. Fuentes-Duculan, I. Novitskaya, A. Khatcherian, M. Bluth, M. Lowes and 1 more. Journal of Experimental Medicine, 2007

650 citations recorded by the source corpus.

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.

Subfields: Dermatology, Immunology, Immunology and Allergy

View Paper: https://www.semanticscholar.org/paper/718e8cc7a54bf8e859051a89c5c6eb20a1ede3ae

How researchers see this paper

The researchers whose trusted networks rank it highest, strongest advocate first. Every researcher gets a different order.

In Dermatology

1. Frank O. Nestle
2. J. Krueger

In Immunology

1. Frank O. Nestle
2. J. Krueger
3. M. Lebwohl
4. A. Di Cesare
5. J. Emer
6. P. Di Meglio
7. Nora Koutruba

Citations in the corpus

• Psoriasis and systemic inflammatory diseases: potential mechanistic links between skin disease and co-morbid conditions. (2010, background): “Furthermore, effective treatment of psoriasis reduces the levels of circulating cytokines such as TNF and IL-1, which, at higher sustained levels, are likely risk factors for cardiovascular disease (CVD) (Zaba et al., 2007).”
• Imiquimod-Induced Psoriasis-Like Skin Inflammation in Mice Is Mediated via the IL-23/IL-17 Axis1 (2009, background): “In patients with psoriasis, amelioration of psoriasis is associated with reduced Th17 responses (26, 27).”
• Circulating Th17, Th22, and Th1 Cells Are Increased in Psoriasis (2009, positive): “These cells and the cytokines produced by these cells are found in increased levels within skin affected by psoriasis (Chan et al., 2006; Wolk et al., 2006; Wilson et al., 2007; Zaba et al., 2007; Kryczek et al., 2008; Lowes et al., 2008; Harper et al., 2009).”
• The IL-23/Th17 axis in the immunopathogenesis of psoriasis. (2009, background): “Finally, the gene expression analysis of IL-17-producing cells identified a unique expression pattern of proinflammatory mediators, including IL-17A, IL-17F, IL-6, CCL20, and GM-CSF (Langrish et al., 2005).”
• Brodalumab, an anti-interleukin-17-receptor antibody for psoriasis. (2012, neutral): “Oral or intramuscular glucocorticoids 5 (13) 4 (10) 3 (8) 4 (10) 5 (12) 16 (10)”
• Review of ustekinumab, an interleukin-12 and interleukin-23 inhibitor used for the treatment of plaque psoriasis (2010, positive): “Recent evidence also suggests that efficacy from TNF-α antagonist therapy may be similar to the mechanism of ustekinumab by downregulating pro-inflammatory pathways in lesional skin.(25,26) Etanercept reduced the inflammatory dendritic cell products that drive Th17 cell proliferation (IL-23), as wel”
• A critical function for transforming growth factor-β, interleukin 23 and proinflammatory cytokines in driving and modulating human TH-17 responses (2008, background): “The T H -17 pathway has been linked to the pathogenesis of several autoimmune diseases, including psoriasi”
• Th17 cells in human disease (2008, background): “Interestingly, a recent study found that etanercept (soluble TNF receptor) rapidly downmodulates expression of many Th17-associated cytokines, including IL-17, IL-22, IL-6, IL-1b, and IL-23, as well as CCL20 and anti-microbial peptides (71).”