Epidermal expression of I‐TAC (Cxc111) instructs adaptive Th2‐type immunity

Epidermal expression of I‐TAC (Cxc111) instructs adaptive Th2‐type immunity
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IâTAC (Cxc111) 的表皮表达指导适应性 Th2â 型免疫

DOI:
10.1096/fj.13-233593
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发表时间:
2014
期刊:
The FASEB Journal
影响因子:
--
通讯作者:
Jan M Ehrchen
Jan M Ehrchen
中科院分区:
--
文献类型:
--
作者:
Kirsten Roebrock;Cord Sunderkötter;Niels-Arne Münck;Marc Wolf;Nadine Nippe;Katarzyna Barczyk;Georg Varga;Thomas Vogl;Johannes Roth;Jan M Ehrchen

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为了破译 Th2 型免疫局部微环境的早期启动子,我们想要鉴定在易感、Th2 倾向的 BALB/c 小鼠受感染皮肤中由利什曼原虫诱导的基因模式,但不包括抗性、Th1 倾向的 C57BL/6 小鼠的感染皮肤。我们发现,在易感小鼠的表皮感染的前 2 天内,趋化因子 I-TAC (Cxc111) 的表达显着上调,而耐药小鼠则没有。因此,在感染第一天对耐药小鼠局部注射 I-TAC (2×1 μg) 会导致 Th2 驱动的疾病持续恶化,并显着提高寄生虫水平。在细胞水平上,I-TAC 减少皮肤引流淋巴结中的树突状细胞 (DC) 和体外 DC 的 IL-12 产生。因此,我们首次证明表皮来源的 I-TAC 会触发持续的 Th2 反应,从而决定复杂免疫过程的结果。-Roebrock, K.、Sunderkotter, C.、Münck, N-A.、Wolf, M.、Nippe, N.、Barczyk, K.、Varga, G.、Vogl, T.、Roth, J., Ehrchen, J. I-TAC (Cxc111) 的表皮表达指导适应性 Th2 型免疫。FASEB J.28, 28–1724 (1734)。 www.fasebj.org
To decipher early promoters of the local microenvironment for Th2‐type immunity, we wanted to identify gene patterns that were induced byLeishmania majorin the infected skin of susceptible, Th2‐prone BALB/c, but not of resistant, Th1‐prone C57BL/6 mice. We found a marked up‐regulation of the chemokine I‐TAC (Cxc111) during the first 2 d of infection in the epidermis of susceptible but not of resistant mice. Accordingly, local injection of I‐TAC (2×1 μg) in resistant mice on the first day of infection resulted in a Th2‐driven, sustained deterioration of disease and dramatically enhanced parasite levels. On the cellular level, I‐TAC decreased IL‐12 production by dendritic cells (DCs) in skin‐draining lymph nodes and by DCsin vitro. Thus, we demonstrate for the first time that epidermis‐derived I‐TAC triggers a sustained Th2‐response that determines the outcome of a complex immunological process.—Roebrock, K., Sunderkotter, C., Münck, N‐A., Wolf, M., Nippe, N., Barczyk, K., Varga, G., Vogl, T., Roth, J., Ehrchen, J. Epidermal expression of I‐TAC (Cxc111) instructs adaptive Th2‐type immunity.FASEB J.28, 28–1724 (1734). www.fasebj.org
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