We found that mechanical injury to mouse skin, which can be caused by tape stripping, results in rapid induction of IL-10 mRNA. IL-10–/– mice were used to examine the role of IL-10 in a mouse model of allergic dermatitis induced by epicutaneous (EC) sensitization with OVA on tape-stripped skin. Skin infiltration by eosinophils and expression of eotaxin, IL-4, and IL-5 mRNA in OVA-sensitized skin sites were severely diminished in IL-10–/– mice. Following in vitro stimulation with OVA, splenocytes from EC-sensitized IL-10–/– mice secreted significantly less IL-4, but significantly more IFN-γ, than splenocytes from WT controls. A similar skewing in cytokine secretion profile was observed in the splenocytes of IL-10–/– mice immunized intraperitoneally with OVA. IL-10–/– APCs skewed the in vitro response of OVA T cell receptor (TCR) transgenic T cells towards Th1. Examination of the Th response of WT and IL-10–/– mice immunized with OVA-pulsed WT or IL-10–/– DCs revealed that both DCs and T cells participate in IL-10 skewing of the Th2 response in vivo. These results suggest that IL-10 plays an important role in the Th2 response to antigen and in the development of skin eosinophilia in a murine model of allergic dermatitis.
Dhafer Laouini, Harri Alenius, Paul Bryce, Hans Oettgen, Erdyni Tsitsikov, Raif S. Geha
Current therapeutic strategies for genetic skin disorders rely on the complex process of grafting genetically engineered tissue to recipient wound beds. Because fibroblasts synthesize and secrete extracellular matrix, we explored their utility in recessive dystrophic epidermolysis bullosa (RDEB), a blistering disease due to defective extracellular type VII collagen. Intradermal injection of RDEB fibroblasts overexpressing type VII collagen into intact RDEB skin stably restored correctly localized type VII collagen expression in vivo and normalized hallmark RDEB disease features, including subepidermal blistering and anchoring fibril defects.
Susana Ortiz-Urda, Qun Lin, Cheryl L. Green, Douglas R. Keene, M. Peter Marinkovich, Paul A. Khavari