Inducible ablation of mouse Langerhans cells diminishes but fails to abrogate contact hypersensitivity

被引:336
作者
Bennett, CL
van Rijn, E
Jung, S
Inaba, K
Steinman, RM
Kapsenberg, ML
Clausen, BE
机构
[1] Univ Amsterdam, Acad Med Ctr, Dept Cell Biol & Histol, NL-1105 AZ Amsterdam, Netherlands
[2] Univ Amsterdam, Acad Med Ctr, Dept Dermatol, NL-1105 AZ Amsterdam, Netherlands
[3] Weizmann Inst Sci, Dept Immunol, IL-76100 Rehovot, Israel
[4] Kyoto Univ, Grad Sch Biostudies, Dept Anim Dev & Physiol, Kyoto 6068502, Japan
[5] Rockefeller Univ, Lab Cellular Physiol & Immunol, New York, NY 10021 USA
基金
英国惠康基金;
关键词
D O I
10.1083/jcb.200501071
中图分类号
Q2 [细胞生物学];
学科分类号
071009 ; 090102 ;
摘要
Langerhans cells (LC) form a unique subset of dendritic cells ( DC) in the epidermis but so far their in vivo functions in skin immunity and tolerance could not be determined, in particular in relation to dermal DC ( dDC). Here, we exploit a novel diphtheria toxin (DT) receptor (DTR)/ DT- based system to achieve inducible ablation of LC without affecting the skin environment. Within 24 h after intra-peritoneal injection of DT into Langerin-DTR mice LC are completely depleted from the epidermis and only begin to return 4 wk later. LC deletion occurs by apoptosis in the absence of inflammation and, in particular, the dDC compartment is not affected. In LC-depleted mice contact hypersensitivity (CHS) responses are significantly decreased, although ear swelling still occurs indicating that dDC can mediate CHS when necessary. Our results establish Langerin-DTR mice as a unique tool to study LC function in the steady state and to explore their relative importance compared with dDC in orchestrating skin immunity and tolerance.
引用
收藏
页码:569 / 576
页数:8
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