Extended DNFB‐induced contact hypersensitivity models display characteristics of chronic inflammatory dermatoses

Abstract

Despite recent developments, there is a high medical need for new treatment options for chronic inflammatory dermatoses like allergic contact dermatitis (ACD) and psoriasis. Particularly, more predictive skin inflammation models are required to facilitate the process of drug discovery. Murine contact hypersensitivity (CHS) models adequately reflect ACD and are also used to characterize therapeutic approaches for psoriasis. Using the hapten 2,4-dinitrofluorobenzene (DNFB), we established new subacute and subchronic DNFB-induced CHS models in C57BL/6 mice, which more closely reflect the characteristics of chronic T-cell-dependent inflammatory dermatoses as pronounced keratinocyte proliferation, strong hypervascularization, immune cell infiltration and overexpression of T cell and inflammatory cytokines. For the subacute DNFB model, we demonstrated anti-inflammatory activity of the glucocorticoid, prednisolone, as well as of neutralization of TNFα, IL-12/IL-23 or IL-18. In the subchronic DNFB-induced CHS model, deficiency for MyD88 and IL-12/IL-35 p35 chain but not IL-12/IL-23 p40 chain led to decreased skin inflammation. Furthermore, as exemplified by the dose-dependently effective therapeutic prednisolone treatment, the subchronic model allows the continuous therapy of a pre-established stable contact dermatitis. Altogether, prolonged DNFB-induced mouse CHS models closely reflect ACD sensitive to glucocorticoids as standard therapy, reveal a more chronic skin inflammation and are responsive to cytokine antagonization.

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

“…BMDCs from Mincle-KO and wild-type mice were differentiated from proliferating mouse bone marrow progenitors according to a previously described protocol (48). A well-known murine model of allergic contact dermatitis was induced using a method described previously (18). Cholesterol sulfate quantification in skin was performed according to a protocol (49) with some modifications.…”

“…Taking into account (i) the significant inducibility of Mincle expression in skin to the topical skin irritation caused by DNFB, a well-known inductor of allergic skin reactions, and (ii) the significantly impaired secretion of proinflammatory mediators in response to a single DNFB application in Mincle-deficient animals, we examined the role of Mincle in the pathogenesis of cutaneous allergic inflammation. To address the role of Mincle in the development of cutaneous allergic inflammation, we used one of the most commonly used models of contact hypersensitivity (CHS) that adequately reflect allergic contact dermatitis (18). Mincle-KO and wild-type mice were sensitized to DNFB on their abdomens, followed by challenges with the same sensitizer on the dorsum of both ears.…”

Sphingolipids and Inflammatory Diseases of the Skin

“…Contact hypersensitivity is one of the most intensively studied animal model to examine immunological mechanisms of AD and to investigate the role of immunomodulators in this disease (Rose et al 2012). Indeed in this model, topically administered S1P inhibited the inflammatory reaction in the sensitization as well as in the elicitation phase (Reines et al 2009).…”

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

“…Allergic contact dermatitis (ACD) is a skin disease caused by an allergic reaction to the allergens in contact with the skin, characterized by redness, papules, vesicles, followed by scaling and dryness [1,2]. Approximately, 15-20% of the population worldwide is affected by this disease [3,4], leading to a loss of 4 million work-days per year and almost $400 million in the United States alone [5][6][7].…”