Abstract
RationaleMast cells, expressing c-kit, are crucial effector cells in allergic and anaphylactic responses. Increased mast cells are found in atopic dermatitis (AD) skin lesions. However, the role of mast cells in AD has not been investigated sufficiently. Inducible selective-expression of IL-13 in mouse skin caused AD-like phenotypes including increased mast cells and mediators. We hypothesized that mast cells play an important role in IL-13-induced AD and tested this using skin-specific IL-13 Tg mice with mast cell deficiency.MethodsTg+/c-kit-/- mice obtained from crossbreeding IL-13 Tg mice with c-kit deficient Kit W-sh/KitW-sh mice were compared with IL-13 Tg mice carrying wild type c-kit (Tg+/c-kit+/+) mice. Skin mast cells in Kit W-sh/KitW-sh mice usually disappear by the age of 13 weeks. The IL-13 transgene in the skin was activated at age of 15 weeks by withdrawal of doxycycline from drinking water. AD clinical scores, scratching numbers were recorded. Skin samples were obtained and analyzed by H&E staining, toluidine blue staining, and ELISA.ResultsAll Tg+/c-kit+/+ mice developed severe AD-like phenotypes by the age of 5 months. Remarkably, only 30% of Tg+/c-kit-/- mice developed mild AD symptoms, which was significantly delayed in onset by 3 months (AD and itching scores). In addition, Tg+/c-kit-/- mice showed significantly decreased eosinophils, decreased levels of TSLP and IL-4 but comparable levels of IFN-γ in the skin compared to Tg+/c-kit+/+ mice.ConclusionThis study suggests that mast cells are important in initiating and maintaining skin inflammation of AD induced by IL-13 probably through induction of TSLP and IL-4. RationaleMast cells, expressing c-kit, are crucial effector cells in allergic and anaphylactic responses. Increased mast cells are found in atopic dermatitis (AD) skin lesions. However, the role of mast cells in AD has not been investigated sufficiently. Inducible selective-expression of IL-13 in mouse skin caused AD-like phenotypes including increased mast cells and mediators. We hypothesized that mast cells play an important role in IL-13-induced AD and tested this using skin-specific IL-13 Tg mice with mast cell deficiency. Mast cells, expressing c-kit, are crucial effector cells in allergic and anaphylactic responses. Increased mast cells are found in atopic dermatitis (AD) skin lesions. However, the role of mast cells in AD has not been investigated sufficiently. Inducible selective-expression of IL-13 in mouse skin caused AD-like phenotypes including increased mast cells and mediators. We hypothesized that mast cells play an important role in IL-13-induced AD and tested this using skin-specific IL-13 Tg mice with mast cell deficiency. MethodsTg+/c-kit-/- mice obtained from crossbreeding IL-13 Tg mice with c-kit deficient Kit W-sh/KitW-sh mice were compared with IL-13 Tg mice carrying wild type c-kit (Tg+/c-kit+/+) mice. Skin mast cells in Kit W-sh/KitW-sh mice usually disappear by the age of 13 weeks. The IL-13 transgene in the skin was activated at age of 15 weeks by withdrawal of doxycycline from drinking water. AD clinical scores, scratching numbers were recorded. Skin samples were obtained and analyzed by H&E staining, toluidine blue staining, and ELISA. Tg+/c-kit-/- mice obtained from crossbreeding IL-13 Tg mice with c-kit deficient Kit W-sh/KitW-sh mice were compared with IL-13 Tg mice carrying wild type c-kit (Tg+/c-kit+/+) mice. Skin mast cells in Kit W-sh/KitW-sh mice usually disappear by the age of 13 weeks. The IL-13 transgene in the skin was activated at age of 15 weeks by withdrawal of doxycycline from drinking water. AD clinical scores, scratching numbers were recorded. Skin samples were obtained and analyzed by H&E staining, toluidine blue staining, and ELISA. ResultsAll Tg+/c-kit+/+ mice developed severe AD-like phenotypes by the age of 5 months. Remarkably, only 30% of Tg+/c-kit-/- mice developed mild AD symptoms, which was significantly delayed in onset by 3 months (AD and itching scores). In addition, Tg+/c-kit-/- mice showed significantly decreased eosinophils, decreased levels of TSLP and IL-4 but comparable levels of IFN-γ in the skin compared to Tg+/c-kit+/+ mice. All Tg+/c-kit+/+ mice developed severe AD-like phenotypes by the age of 5 months. Remarkably, only 30% of Tg+/c-kit-/- mice developed mild AD symptoms, which was significantly delayed in onset by 3 months (AD and itching scores). In addition, Tg+/c-kit-/- mice showed significantly decreased eosinophils, decreased levels of TSLP and IL-4 but comparable levels of IFN-γ in the skin compared to Tg+/c-kit+/+ mice. ConclusionThis study suggests that mast cells are important in initiating and maintaining skin inflammation of AD induced by IL-13 probably through induction of TSLP and IL-4. This study suggests that mast cells are important in initiating and maintaining skin inflammation of AD induced by IL-13 probably through induction of TSLP and IL-4.
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