Role of Th17 Cells in Skin Inflammation of Allergic Contact Dermatits

Abstract

Extending the classical concept considering an imbalance exclusively of T helper(h) 1 and Th2 cells on the bottom of many inflammatory diseases, Th17 cells were recently described. Today, there is sufficient experimental evidence to classify psoriasis and allergic contact dermatitis (ACD) amongst other inflammatory skin disorders as IL-17 associated diseases. In several human studies, T-cell-clones could be isolated from eczema biopsies, and high IL-17 levels were observed after challenge with allergen. In the last years, the phenotype of these IL-17 releasing T cells was in the focus of discussion. It has been suggested that Th17 could be identified by expression of retinoic acid receptor-related orphan receptor (ROR)C (humans) or RORγt (mice) and IL-17, accompanied by the absence of IFN-γ and IL-22. In cells from skin biopsies, contact allergens elevate IL-17A, IL-23, and RORC within the subset of Th cells. The indications for a participation of Th17 in the development of ACD are supported by data from IL-17 deficient mice with reduced contact hypersensitivity (CHS) reactions that could be restored after transplantation of wild type CD4+ T cells. In addition to Th17 cells, subpopulations of CD8+ T cells and regulatory T cells are further sources of IL-17 that play important roles in ACD as well. Finally, the results from Th17 cell research allow today identification of different skin diseases by a specific profile of signature cytokines from Th cells that can be used as a future diagnostic tool.

Receptor Mincle promotes skin allergies and is capable of recognizing cholesterol sulfate

“…We found in allergic inflamed ears from Mincle-KO mice a suppressed production of IL-17A, which is regarded as a signature cytokine for Th17 cells (38). Th17 cells play a crucial role as effector cells in the pathogenesis of allergic contact dermatitis, psoriasis, and autoimmune diseases (39)(40)(41). Thus, the activation of Mincle during the development of allergic contact dermatitis may lead to a bias that influences T-cell polarization.…”

Obaculactone exerts a novel ameliorating effect on contact dermatitis through regulating T lymphocyte

“…IL-2 is able to enhance the activation and proliferation of T cells [18], while IFN-γ is considered to stimulate macrophages [19]. In addition, the other important pro-inflammatory cytokines, such as TNF-α and IL-17a, are also involved in hypersensitivity responses [20][21][22]. Our data indicated that obaculactone could reduce the mRNA levels of IL-2, IFN-γ, TNF-α and IL-17a (Fig.…”

Oral administration of paeoniflorin attenuates allergic contact dermatitis by inhibiting dendritic cell migration and Th1 and Th17 differentiation in a mouse model

“…Experiments for ACD control have focused on prevention of DC migration, inhibition of Th1/Th2/Th17 responses and reduction of local inflammatory cytokine products [12,14]. Attempts to modulate the immune response to ACD have been conducted in a number of clinical trials but have achieved only limited success [15].…”