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Sci Immunol. 2016 Sep 23;1(3):eaaf8665. doi: 10.1126/sciimmunol.aaf8665.

Arc/Arg3.1 governs inflammatory dendritic cell migration from the skin and thereby controls T cell activation.

Author information

1
Institut für Neuroimmunologie und Multiple Sklerose, Zentrum für Molekulare Neurobiologie Hamburg, Universitätsklinikum Hamburg-Eppendorf, 20251 Hamburg, Germany.
2
Institut Curie, PSL Research University, CNRS, UMR 144, 75005 Paris, France.
3
Fraunhofer-Institut für Molekularbiologie und Angewandte Oekologie IME, ScreeningPort, 22525 Hamburg, Germany.
4
Institut für Molekulare und Zelluläre Kognition, Zentrum für Molekulare Neurobiologie Hamburg, Universitätsklinikum Hamburg-Eppendorf, 20251 Hamburg, Germany.
5
Microarray and Deep-Sequencing Core Facility, Universitätsmedizin Göttingen, 37077 Göttingen, Germany.
6
Institut für Neuroimmunologie und Multiple Sklerose, Zentrum für Molekulare Neurobiologie Hamburg, Universitätsklinikum Hamburg-Eppendorf, 20251 Hamburg, Germany. manuel.friese@zmnh.uni-hamburg.de.

Abstract

Skin-migratory dendritic cells (migDCs) are pivotal antigen-presenting cells that continuously transport antigens to draining lymph nodes and regulate immune responses. However, identification of migDCs is complicated by the lack of distinguishing markers, and it remains unclear which molecules determine their migratory capacity during inflammation. We show that, in the skin, the neuronal plasticity molecule activity-regulated cytoskeleton-associated protein/activity-regulated gene 3.1 (Arc/Arg3.1) was strictly confined to migDCs. Mechanistically, Arc/Arg3.1 was required for accelerated DC migration during inflammation because it regulated actin dynamics through nonmuscle myosin II. Accordingly, Arc/Arg3.1-dependent DC migration was critical for mounting T cell responses in experimental autoimmune encephalomyelitis and allergic contact dermatitis. Thus, Arc/Arg3.1 was restricted to migDCs in the skin and drove fast DC migration by exclusively coordinating cytoskeletal changes in response to inflammatory challenges. These findings commend Arc/Arg3.1 as a universal switch in migDCs that may be exploited to selectively modify immune responses.

PMID:
28783680
DOI:
10.1126/sciimmunol.aaf8665

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