Hironori Matsushima1, Satoru Hayashi, Shinji Shimada. 1. Department of Dermatology, Faculty of Medicine, University of Yamanashi 1110, Shimokato, Tamaho, Nakakoma, Yamanashi, 409-3898, Japan.
Abstract
BACKGROUND: The balance between Th1 and Th2 subsets is important with respects to susceptibility and resistance to particular infection or autoimmune diseases. However, the mechanism controlling Th1/Th2 balance remains unclear, although several factors have been reported to induce Th1/Th2 differentiation. Atopic Dermatitis (AD) that is a chronic skin disorder has been known as Th2 biased nature characterized by high expression of IgE in the serum. In contrast, the chronic skin lesions express IFNgamma and some patients don't show IgE in the serum. Thus, the pathology is also complicated now. OBJECTIVE: We focused on skin scratching that is common feature in the patients. In this study, we investigated in order to determine whether skin scratching regulates immune responses in murine epicutaneous sensitization model. METHODS: The scratched mice on abdominal skin using wire brush were applied with keyhole limpet hemocyanin (KLH) on the skin using occlusive patch. We examined the immune responses including delayed type hypersensitivity (DTH) reaction, antigen-specific serum immunoglobulin formation, and cytokine expressions on the local skin in comparison with mice without scratching. RESULTS: We found that the epicutaneously sensitized mice with KLH on abdominal skin showed Th2 biased immune response including expression of antigen-specific IgE in the serum and IL-13 in the local skin. Surprisingly, scratching on local abdominal skin using wire brush exchanged the immune response from Th2 dominance to Th1, because the mice displayed DTH reaction and significant level of antigen-specific IgG2a and IgG2b but not IgE in the serum. Furthermore, the abdominal skin showed significant level of IFNgamma but not IL-13. CONCLUSION: These data demonstrate that skin scratching switches immune response from Th2 biased response to Th1. This suggests that skin scratching play critical roles as one of exogenous immune modulator. This murine sensitization model may help to understand natures of several allergic disorders including AD.
BACKGROUND: The balance between Th1 and Th2 subsets is important with respects to susceptibility and resistance to particular infection or autoimmune diseases. However, the mechanism controlling Th1/Th2 balance remains unclear, although several factors have been reported to induce Th1/Th2 differentiation. Atopic Dermatitis (AD) that is a chronic skin disorder has been known as Th2 biased nature characterized by high expression of IgE in the serum. In contrast, the chronic skin lesions express IFNgamma and some patients don't show IgE in the serum. Thus, the pathology is also complicated now. OBJECTIVE: We focused on skin scratching that is common feature in the patients. In this study, we investigated in order to determine whether skin scratching regulates immune responses in murine epicutaneous sensitization model. METHODS: The scratched mice on abdominal skin using wire brush were applied with keyhole limpet hemocyanin (KLH) on the skin using occlusive patch. We examined the immune responses including delayed type hypersensitivity (DTH) reaction, antigen-specific serum immunoglobulin formation, and cytokine expressions on the local skin in comparison with mice without scratching. RESULTS: We found that the epicutaneously sensitized mice with KLH on abdominal skin showed Th2 biased immune response including expression of antigen-specific IgE in the serum and IL-13 in the local skin. Surprisingly, scratching on local abdominal skin using wire brush exchanged the immune response from Th2 dominance to Th1, because the mice displayed DTH reaction and significant level of antigen-specific IgG2a and IgG2b but not IgE in the serum. Furthermore, the abdominal skin showed significant level of IFNgamma but not IL-13. CONCLUSION: These data demonstrate that skin scratching switches immune response from Th2 biased response to Th1. This suggests that skin scratching play critical roles as one of exogenous immune modulator. This murine sensitization model may help to understand natures of several allergic disorders including AD.