Atopic dermatitis and functional barrier defects

Approximately 20% of all children in the Western countries suffer from atopic dermatitis. It is a chronic, relapsing inflammatory, itching and eczematous disease. Children are affected psychologically and socially and may experience difficulties at school and in their social life; they also have an increased risk for infections of the skin and development of type I allergies.

During the last five years, research in this disease has been focused on the function of the skin barrier. A milestone discovery was made in 2005 when it was shown that stop mutations in the FLG gene, which codes for filaggrin, was found in up to 1/3 of all patients with atopic dermatitis.

Our research has shown that inflammatory cytokines belonging to both the Th1 and Th2 profile down-regulate the expression of filaggrin as well as other structural proteins in the skin. We have also shown that the activity and expression of the upstream regulator of filaggrin maturation, Caspase 14, is down-regulated by inflammatory reactions dominated by both Th1 and Th2.

Inflammation in the skin by atopic dermatitis can down-regulate the expression and maturation of the structural skin barrier protein filaggrin.

Ongoing projects

• The effect of Th₁ and Th₂ inducing cytokines on skin barrier function including:
  • Filaggrin expression and maturation
  • Other structural proteins such as involucrine and loricrine
• The role of the alarmins IL-33 and HgMB1 in the inflammatory reaction of the skin
• The role of CD8+ lymphocytes in inflammatory skin reaction
• The immunoregulatory axis OX40/OX40L in the pathogenesis of atopic dermatitis

Methods

• Animal models for AD
• Cell cultures (single layer keratinocytes, lymphocytes, #D skin)
• Q-RT-PCR, Western blot, ELISA
• Histology, Immunohistochemistry

International collaborations in the UK, the US, Holland, Germany, France, Japan, and Korea.

Milestone publications

Vestergaard C, Hvid M, Johansen C, Kemp K, Deleuran B, Deleuran M: Inflammation-induced alterations in the skin barrier function: implications in atopic dermatitis. Chem Immunol Allergy 2012, 96:77-80.

Deleuran MS, Vestergaard C: Therapy of severe atopic dermatitis in adults. J Dtsch Dermatol Ges 2012.

Deleuran M, Hvid M, Kemp K, Christensen GB, Deleuran B, Vestergaard C: IL-25 induces both inflammation and skin barrier dysfunction in atopic dermatitis. Chem Immunol Allergy 2012, 96:45-49.

Hvid M, Vestergaard C, Kemp K, Christensen GB, Deleuran B, Deleuran M: IL-25 in atopic dermatitis: a possible link between inflammation and skin barrier dysfunction? The Journal of investigative dermatology 2011, 131(1):150-157.

Hvid M, Johansen C, Deleuran B, Kemp K, Deleuran M, Vestergaard C: Regulation of caspase 14 expression in keratinocytes by inflammatory cytokines--a possible link between reduced skin barrier function and inflammation? Experimental dermatology 2011, 20(8):633-636.

Christensen GB, Hvid M, Kvist PH, Deleuran B, Deleuran M, Vestergaard C, Kemp K: CD4(+) T cell depletion changes the cytokine environment from a T(H)1/T(H)2 response to a T(C)17-like response in a murine model of atopic dermatitis. Int Immunopharmacol 2011, 11(9):1285-1292.

Hvid M, Jensen HK, Deleuran B, Kemp K, Andersson C, Deleuran M, Vestergaard C: Evaluation of FITC-induced atopic dermatitis-like disease in NC/Nga mice and BALB/c mice using computer-assisted stereological toolbox, a computer-aided morphometric system. Int Arch Allergy Immunol 2009, 149(3):188-194.