Article

A tale of two plaques: Convergent mechanisms of T-cell-mediated inflammation in psoriasis and atherosclerosis

Dermatology Clinical Research Unit, Teledermatology Program, Department of Dermatology, University of California, 3301 C St., Suite 1400, Sacramento, Davis, CA 95816, USA.
Experimental Dermatology (Impact Factor: 4.12). 07/2011; 20(7):544-9. DOI: 10.1111/j.1600-0625.2011.01308.x
Source: PubMed

ABSTRACT Psoriasis and atherosclerosis are diseases in which effector T lymphocytes such as Helper T cells type 1 (Th1) and 17 (Th17) play integral roles in disease pathogenesis and progression. Regulatory T cells (Treg) also exert clinically important anti-inflammatory effects that are pathologically altered in psoriasis and atherosclerosis. We review the immunological pathways involving Th1, Th17 and Treg cells that are common to psoriasis and atherosclerosis. These shared pathways provide the basis for mechanisms that may explain the epidemiologic observation that patients with psoriasis have an increased risk of heart disease. Improved understanding of these pathways will guide future experiments and may lead to the development of therapeutics that prevent or treat cardiovascular complications in patients with psoriasis.

Download full-text

Full-text

Available from: Ehrin J Armstrong, Nov 28, 2014
1 Follower
 · 
116 Views
  • Source
    • "Caspase-14 Protects against Parakeratosis key importance for the development of psoriatic lesions (reviewed in Armstrong et al., 2011), but no difference was observed in infiltrating leukocyte or T-cell numbers between IMQ-treated WT and caspase-14 À / À skin. The difference in parakeratotic plaque formation in caspase-14-deficient skin was not due solely to the IMQ treatment, because an increase, although less extensive, in epidermal thickness, parakeratosis, and TEWL was also observed upon topical treatment of these mice with vehicle cream, which was not the case in control mice (Figure 6). "
    [Show abstract] [Hide abstract]
    ABSTRACT: Caspase-14 is an important protease in the proper formation of a fully functional skin barrier. Newborn mice that are deficient in caspase-14 exhibit increased transepidermal water loss and are highly sensitive to UVB-induced photodamage. Decreased caspase-14 expression and incomplete caspase-14 processing in lesional psoriatic parakeratotic stratum corneum has been reported previously. In this study, we show that caspase-14-deficient skin frequently displays incompletely cornified cells in the transitional zone between the granular and the cornified layers, pointing to a delay in cornification. We also demonstrate that after challenge of epidermal permeability barrier function by repetitive acetone treatment, a higher incidence of large parakeratotic plaques was observed in caspase-14-deficient skin. Furthermore, caspase-14-deficient mice are more prone than control mice to the development of parakeratosis upon induction of psoriasis-like dermatitis by imiquimod treatment. These results show that lack of caspase-14 expression predisposes to the development of parakeratosis and that caspase-14 has an important role in keratinocyte terminal differentiation and the maintenance of normal stratum corneum, especially in conditions causing epidermal hyperproliferation.Journal of Investigative Dermatology advance online publication, 27 September 2012; doi:10.1038/jid.2012.350.
    Journal of Investigative Dermatology 09/2012; 133(3). DOI:10.1038/jid.2012.350 · 6.37 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: Psoriasis ist eine genetisch determinierte, chronisch entzündliche Systemerkrankung. Neben charakteristischen Hautmanifestationen treten insbesondere bei mittelschwer bis schwer betroffenen Patienten andere Erkrankungen gehäuft auf. Diese begleitend auftretenden Erkrankungen werden als Komorbiditäten bezeichnet. Metabolische Erkrankungen (wie z. B. Diabetes mellitus, Insulinresistenz, Fettstoffwechselstörungen, meist auf der Grundlage einer Adipositas) und kardiovaskuläre Erkrankungen (wie z. B. arterieller Hypertonus, koronare Herzkrankheit, Myokardinfarkt und Apoplex) sind dabei von besonderer Bedeutung, da sie auch die Mortalität der Patienten beeinflussen können. Aber auch psychiatrische Erkrankungen sind bei Psoriasispatienten häufig und beeinflussen das Therapiemanagement. Der Dermatologe ist in den meisten Fällen der erste Ansprechpartner von Psoriasispatienten und somit die Schlüsselfigur im Therapiemanagement. Er ist dabei auch für die Früherkennung und Therapiesteuerung von Komorbiditäten mitverantwortlich. Die von ihm durchgeführte antipsoriatische Therapie muss mit den vorliegenden Komorbiditäten und deren medikamentösen Therapien abgestimmt werden. Der folgende Beitrag stellt den aktuellen Wissensstand über die psoriatischen Komorbiditäten und ihre Konsequenzen für die Praxis dar.
    Der Hautarzt 03/2012; 63(3). DOI:10.1007/s00105-011-2230-x · 0.54 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Aim  Increased frequency of cardiovascular disease and its possible relations with insulin resistance have been reported in patients with inflammatory diseases. The aim of our study was to investigate insulin resistance and serum adiponectin levels as cardiovascular risk markers in patients with Behçet's disease. Method  Study population consisted of 40 patients with Behçet's disease (BD) and a control group composed of age, gender, body mass index-matched 46 healthy individuals. All patients were examined for signs of Behçet's disease. Body mass index, waist and hip circumference were measured. Insulin resistance was evaluated using the homeostasis model assessment-insulin resistance method. Erythrocyte sedimentation rate (ESR), lipid profile, high sensitive CRP (hsCRP), adiponectin, TNF-α, IL-6 and IL-8 levels were measured. Results  Erythrocyte sedimentation rate, serum hsCRP and IL-6 levels were significantly higher in patients with BD than those in the controls (P = 0.001, P = 0.001, P = 0.001, respectively). Fasting plasma glucose, insulin levels and lipid profile were not different between the two groups. Insulin resistance and decreased levels of the serum adiponectin were not detected in the patients. There was no relationship between insulin resistance, adiponectin levels and inflammatory markers. Active and inactive patients did not differ in respect of any parameters. Conclusion  Being a systemic vasculitis, BD may cause cardiovascular involvement. In this study, dyslipidemia, insulin resistance and low adiponectin levels were not detected among our patients with Behçet's disease. Our results suggest that there exists no increased risk for atherosclerotic cardiovascular disease associated with adiponectin levels and insulin resistance in patients with Behçet's disease.
    Journal of the European Academy of Dermatology and Venereology 10/2011; 26(12). DOI:10.1111/j.1468-3083.2011.04318.x · 3.11 Impact Factor
Show more