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

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Science Immunology  23 Sep 2016:
Vol. 1, Issue 3, pp. eaaf8665
DOI: 10.1126/sciimmunol.aaf8665

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Dendritic cell migration reform

Dendritic cells are the messengers of the immune system, transporting antigens from sites of inflammation to the lymph organs that serve as central hubs for immune activation. Ufer et al. have identified a neuronal plasticity molecule—activity-regulated cytoskeleton-associated protein/activity-regulated gene 3.1 (Arc/Arg3.1)—that is expressed in migratory dendritic cells in the skin. Arc/Arg3.1 regulates cytoskeletal changes in dendritic cells, accelerating migration in response to inflammation. Moreover, Arc/Arg3.1 was required for inducing T cell responses in two different disease models—experimental autoimmune encephalitis and allergic contact dermatitis. Targeting Arc/Arg3.1 may therefore be a therapeutic strategy to modify dendritic cell immunotherapy.


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.

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