Division of Immunology, Children's Hospital and Department of Pediatrics, Harvard Medical School, Boston, Mass 02115, USA.
J Allergy Clin Immunol. 2010 Nov;126(5):976-84, 984.e1-5. doi: 10.1016/j.jaci.2010.08.041.
Atopic dermatitis is characterized by scratching and by T(H)2-dominated immune response to cutaneously introduced antigens. Antigen application to skin mechanically injured by tape stripping results in T(H)2-dominated skin inflammation.
To examine the effect of tape stripping on the capacity of skin dendritic cells (DCs) to polarize T cells toward a T(H)2 phenotype.
CD11c(+) DCs were isolated from skin of BALB/c or C57BL/6 mice. Fluorescein isothiocyanate (FITC)(+) and FITC(-) DCs were isolated from draining lymph nodes (DLNs) 24 hours after painting the skin with FITC. DCs were assessed for their ability to induce cytokine secretion by ovalbumin-stimulated naive CD4(+) T cells from T cell receptor-ovalbumin transgenic DO11.10 mice. Cytokine mRNA levels were examined by quantitative PCR.
Dendritic cells isolated from the skin of wild-type, but not thymic stromal lymphopoietin (TSLP) receptor(-/-) or IL-10(-/-), mice 6 hours after tape stripping elicited significantly more IL-4 and IL-13 and significantly less IFN-γ production by CD4(+) cells than DCs isolated from unmanipulated skin, and expressed significantly more mRNA for the T(H)2 skewing molecules IL-10, Jagged1, and Jagged2, but significantly less mRNA for the T(H)1 skewing cytokine IL-12. CD11c(+)FITC(+) cells isolated from DLNs of shaved and tape stripped skin of wild-type, but not TSLP receptor(-/-) or IL-10(-/-), mice polarized T cells significantly more toward T(H)2 and expressed significantly more IL-10, Jagged1, and Jagged2 mRNA than CD11c(+)FITC(+) cells isolated from DLNs of shaved skin. Tape stripping significantly increased TSLP levels in the skin, and TSLP was shown to play an essential role in the T(H)2 polarization of skin DCs by tape stripping.
Tape stripping upregulates TSLP levels in the skin, which polarizes skin DCs to elicit a T(H)2 response via the induction of IL-10.
特应性皮炎的特征是搔抓和 T(H)2 主导的免疫应答，这些免疫应答针对的是皮肤中引入的抗原。抗原应用于通过胶带剥离机械损伤的皮肤会导致 T(H)2 主导的皮肤炎症。
检查胶带剥离对皮肤树突状细胞 (DC) 将 T 细胞向 T(H)2 表型极化的能力的影响。
从 BALB/c 或 C57BL/6 小鼠的皮肤中分离出 CD11c(+) DC。在皮肤涂抹异硫氰酸荧光素 (FITC) 24 小时后，从引流淋巴结 (DLN) 中分离出 FITC(+)和 FITC(-)DC。评估 DC 诱导卵清蛋白刺激的 DO11.10 小鼠 T 细胞受体-卵清蛋白转基因幼稚 CD4(+)T 细胞产生细胞因子的能力。通过定量 PCR 检查细胞因子 mRNA 水平。
与未处理皮肤分离的 DC 相比，野生型小鼠皮肤在胶带剥离后 6 小时分离的 DC 显著增加了 CD4(+)细胞产生的 IL-4 和 IL-13，显著减少了 IFN-γ 的产生，并且表达了更多的 T(H)2 偏倚分子 IL-10、Jagged1 和 Jagged2，而表达了更少的 T(H)1 偏倚细胞因子 IL-12。从野生型小鼠剃毛和胶带剥离皮肤的 DLN 中分离的 CD11c(+)FITC(+)细胞显著地将 T 细胞向 T(H)2 极化，并且表达了更多的 IL-10、Jagged1 和 Jagged2 mRNA，与从剃毛皮肤的 DLN 中分离的 CD11c(+)FITC(+)细胞相比。胶带剥离显著增加了皮肤中的 TSLP 水平，并且 TSLP 被证明在通过诱导 IL-10 使皮肤 DC 向 T(H)2 极化方面发挥了重要作用。
胶带剥离上调皮肤中的 TSLP 水平，通过诱导 IL-10 将皮肤 DC 极化以引发 T(H)2 反应。
