Alefacept (anti-CD2) causes a selective reduction in circulating effector memory T cells (Tem) and relative preservation of central memory T cells (Tcm) in psoriasis

<p>Abstract</p> <p>Background</p> <p>Alefacept (anti-CD2) biological therapy selectively targets effector memory T cells (Tem) in psoriasis vulgaris, a model Type 1 autoimmune disease.</p> <p>Methods</p> <p>Circulating leukocytes were phenotyped in patients receiving alefacept for moderate to severe psoriasis.</p> <p>Results</p> <p>In all patients, this treatment caused a preferential decrease in effector memory T cells (CCR7^-CD45RA^-) (mean 63% reduction) for both CD4⁺and CD8⁺Tem, while central memory T cells (Tcm) (CCR7⁺CD45RA^-) were less affected, and naïve T cells (CCR7⁺CD45RA⁺) were relatively spared. Circulating CD8⁺effector T cells and Type 1 T cells (IFN-γ-producing) were also significantly reduced.</p> <p>Conclusion</p> <p>Alefacept causes a selective reduction in circulating effector memory T cells (Tem) and relative preservation of central memory T cells (Tcm) in psoriasis.</p

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 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

Modulation of inflammatory gene transcripts in psoriasis vulgaris: Differences between ustekinumab and etanercept

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Alefacept (anti-CD2) causes a selective reduction in circulating effector memory T cells (Tem) and relative preservation of central memory T cells (Tcm) in psoriasis-0

<p><b>Copyright information:</b></p><p>Taken from "Alefacept (anti-CD2) causes a selective reduction in circulating effector memory T cells (Tem) and relative preservation of central memory T cells (Tcm) in psoriasis"</p><p>http://www.translational-medicine.com/content/5/1/27</p><p>Journal of Translational Medicine 2007;5():27-27.</p><p>Published online 7 Jun 2007</p><p>PMCID:PMC1906741.</p><p></p

Homeostatic Tissue Responses in Skin Biopsies from NOMID Patients with Constitutive Overproduction of IL-1β

<div><p>The autoinflammatory disorder, <u>N</u>eonatal-<u>o</u>nset <u>M</u>ultisystem <u>I</u>nflammatory <u>D</u>isease (NOMID) is the most severe phenotype of disorders caused by mutations in <em>CIAS1</em> that result in increased production and secretion of active IL-1β. NOMID patients present with systemic and organ-specific inflammation of the skin, central nervous system and bone, and respond dramatically to treatment with IL-1 blocking agents. We compared the cellular infiltrates and transcriptome of skin biopsies from patients with NOMID (n = 14) before treatment (lesional (LS) and non-lesional (pre-NL) skin) and after treatment (post-NL) with the IL-1 blocker anakinra (recombinant IL-1 receptor antagonist, Kineret®, Swedish Orphan Biovitrum AB, SOBI), to normal skin (n = 5) to assess tissue responses in the context of untreated and treated disease. Abundant neutrophils distinguish LS skin from pre-NL and post-NL skin. CD11c⁺ dermal dendritic cells and CD163⁺ macrophages expressed activated caspase-1 and are a likely source of cutaneous IL-1 production. Treatment with anakinra led to the disappearance of neutrophils, but CD3⁺ T cells and HLA-DR⁺ cells remained elevated. Among the upregulated genes IL-6, IL-8, TNF, IL-17A, CCL20, and the neutrophil defensins DEFA1 and DEFA3 were differentially regulated in LS tissues (compared to normal skin). Important significantly downregulated pathways in LS skin included IL-1R/TLR signaling, type I and II cytokine receptor signaling, mitochondrial dysfunction, and antigen presentation. The differential expression and regulation of microRNAs and pathways involved in post-transcriptional modification were suggestive of epigenetic modification in the chronically inflamed tissue. Overall, the dysregulated genes and pathways suggest extensive “adaptive” mechanisms to control inflammation and maintain tissue homeostasis, likely triggered by chronic IL-1 release in the skin of patients with NOMID.</p> </div