Phthalate ester‐induced thymic stromal lymphopoietin mediates allergic dermatitis in mice

Abstract

SummaryRecently air pollutants and irritants have been labelled as possible exogenous risk factors for allergic disorders. Although the underlying causes of allergic disorders such as atopic dermatitis and asthma remain unclear, the T helper type 2 (Th2) cell-mediated allergic inflammatory cascade may contribute to their pathogenesis. In the last decade, it has been documented that one of the candidates for triggering Th2 commitment is thymic stromal lymphopoietin (TSLP), the expression of which is up-regulated in the lesions of allergic patients. Here, we describe TSLP function in a fluorescein isothiocyanate (FITC) -induced contact hypersensitivity (CHS) model. A cytokine profile indicated that the model was dominantly mediated by the Th2 milieu. Interestingly, TSLP was increased in the skin during the sensitization phase when stimulated by a solvent, dibutyl phthalate (DBP), but not by FITC hapten or another solvent, acetone. Ear swelling in FITC-induced CHS was totally abrogated by removing DBP from the sensitization or elicitation phase, and was restored by complementary injection of TSLP. Inversely, the ear swelling was suppressed by injection of small interfering RNA against TSLP during the sensitization phase, which was concomitant with decreasing expression of interleukin-4 at the swollen skin site. Taken together, DBP-induced TSLP during the sensitization phase plays a role in establishing FITC-induced CHS and may be one of the causes of Th2 commitment in the model, suggesting that certain environmental toxins, such as DBP, may endow pro-allergic and atopic predisposition in humans or animals.

A multistrain probiotic formulation attenuates skin symptoms of atopic dermatitis in a mouse model through the generation of CD4+Foxp3+T cells

“…Moreover, TSLP is one of the candidates for triggering Th2 commitment by activating DCs that induce differentiation of naïve T cells to Th2 cells, the expression of which is upregulated in AD-like skin lesions (19). TSLP from KCs induces the expression of Th2 chemokines TARC and macrophage-derived chemokine (MDC).…”

Exacerbation of Allergic Diseases by Chemicals: Role of TSLP

“…Shigeno et al demonstrated that DBP induced TSLP production, which was required in the sensitization and elicitation phases for the migration of antigen-presenting cells to the lymph nodes and ear swelling in a fluorescein isothiocyanate (FITC)-induced contact hypersensitivity model (32). The development of Th2-type responses induced by FITC and DBP was shown to be markedly decreased in TSLPR-deficient mice (33).…”

Long-term dermal exposure to diisononyl phthalate exacerbates atopic dermatitis through oxidative stress in an FITC-induced mouse model

“…Skin sensitization and application to ears with 0.5% FITC were performed in acetone-based solvent, in which acetone and DBP (1:1 ratio) were always present. DBP was used in this study as an immune adjuvant, and previous study has shown that acute or long-term skin exposed to DBP alone did not induced AD (Shigeno et al, 2009;. Hence, DBP could not disturb the effect of DINP in this study.…”