Mechanical injury polarizes skin dendritic cells to elicit a T(H)2 response by inducing cutaneous thymic stromal lymphopoietin expression.
Mechanical injury polarizes skin dendritic cells to elicit a T(H)2 response by inducing cutaneous thymic stromal lymphopoietin expression.
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DOI：
10.1016/j.jaci.2010.08.041
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发表时间：
2010-11
影响因子：
14.2
通讯作者：
Geha, Raif S.
中科院分区：
文献类型：
--
作者：
Oyoshi, Michiko K.;Larson, Ryan P.;Ziegler, Steven F.;Geha, Raif S.
特应性皮炎（AD）的特征是强烈的抓挠和Th 2主导的系统性和局部免疫应答，所述系统性和局部免疫应答是针对外源性抗原的。由于抓挠对皮肤造成机械损伤，我们研究了胶带剥离造成的机械损伤对皮肤树突状细胞（DC）向Th 2表型转移T细胞的能力的影响。与从未处理的皮肤分离的DC相比，胶带剥离后6小时从皮肤分离的DC引起显著更高的IL-4和IL-13的产生，以及显著更低的OVA刺激的CD 4 + D0.11.10细胞的干扰素-γ（IFN-γ）的产生，并且表达显著更多的Th 2偏斜分子IL-10和Notch配体Jagged 1和Jagged 2的mRNA，但Th 1偏斜细胞因子IL-12的mRNA显著较少。在用FITC涂抹后24小时，从剃毛和胶带剥离的小鼠皮肤的引流淋巴结（DLN）分离的CD 11 c +FITC+细胞比从剃毛的非胶带剥离的皮肤的DLN分离的CD 11 c +FITC+细胞显著更多地使T细胞向Th 2极化，并且表达显著更多的IL-10、Jagged 1和Jagged 2 mRNA，但显著更少的IL-12 mRNA。胶带剥离显著增加了皮肤中的TSLP水平。在TSLPR−/−小鼠中的研究表明，TSLP在胶带剥离对皮肤DC的Th 2极化效应中发挥重要作用。这些结果表明，机械损伤造成的抓挠AD患者极化皮肤DCs引发的Th 2反应，通过上调TSLP的局部表达。
Atopic dermatitis (AD) is characterized by intense scratching and a Th2 dominated systemic and local immune response to cutaneously introduced antigens. Because scratching inflicts mechanical injury to the skin, we examined the effect of mechanical injury inflicted by tape stripping on the capacity of skin dendritic cells (DCs) to polarize T cells towards a Th2 phenotype. DCs isolated from skin 6 hrs after tape stripping elicited significantly higher production of IL-4 and IL-13, and significantly lower production of interferon-γ (IFN-γ) by OVA stimulated CD4+ DO.11.10 cells, than DCs isolated from unmanipulated skin, and expressed significantly more mRNA for the Th2 skewing molecules IL-10 and the Notch ligands Jagged1 and Jagged2, but significantly less mRNA for the Th1 skewing cytokine IL-12. CD11c+FITC+ cells isolated from draining lymph nodes (DLN) of shaved and tape stripped mouse skin 24 hrs after painting with FITC polarized T cells towards Th2 significantly more than CD11c+FITC+ cells isolated from DLN of shaved non tape stripped skin, and expressed significantly more IL-10, Jagged1 and Jagged2 mRNA, but significantly less IL-12 mRNA. Tape stripping significantly increased TSLP levels in the skin. Studies in TSLPR−/− mice demonstrated that TSLP played an essential role in the Th2 polarization effect of tape stripping on skin DCs. These results suggest that mechanical injury inflicted by scratching in patients with AD polarizes skin DCs to elicit a Th2 response by upregulating local expression of TSLP.
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DOI：
10.1084/jem.20062211
发表时间：
2007-02-19
期刊：
The Journal of experimental medicine
影响因子：
--
作者：
Allakhverdi Z;Comeau MR;Jessup HK;Yoon BR;Brewer A;Chartier S;Paquette N;Ziegler SF;Sarfati M;Delespesse G
通讯作者：
Delespesse G
影响因子：
4.4
作者：
Krawczyk, Connie M.;Sun, Jie;Pearce, Edward J.
通讯作者：
Pearce, Edward J.
影响因子：
14.2
作者：
Novak, N;Bieber, T
通讯作者：
Bieber, T
DOI：
10.1073/pnas.0801532105
发表时间：
2008-08-19
影响因子：
11.1
作者：
He, Rui;Oyoshi, Michiko K.;Geha, Raif S.
通讯作者：
Geha, Raif S.
DOI：
10.1073/pnas.0507385102
发表时间：
2005-10-11
影响因子：
11.1
作者：
Li, M;Messaddeq, N;Chambon, P
通讯作者：
Chambon, P