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1.
Eur J Immunol ; 49(5): 724-736, 2019 05.
Artículo en Inglés | MEDLINE | ID: mdl-30786014

RESUMEN

The key function of migratory dendritic cells (migDCs) is to take up antigens in peripheral tissues and migrate to draining lymph nodes (dLN) to initiate immune responses. Recently, we discovered that in the mouse immune system activity-regulated cytoskeleton associated protein/activity-regulated gene 3.1 (Arc/Arg3.1) is exclusively expressed by migDCs and is a central driver of fast inflammatory migration. However, the frequency of Arc/Arg3.1-expressing cells in different migDC subsets and Langerhans cells (LCs), their phylogenetic origin, transcription factor dependency, and functional role remain unclear. Here, we found that Arc/Arg3.1+ migDCs derived from common DC precursors and radio-resistant LCs. We detected Arc/Arg3.1+ migDCs in varying frequencies within each migDC subset and LCs. Consistently, they showed superiority in inflammatory migration. Arc/Arg3.1 expression was independent of the transcription factors Irf4 or Batf3 in vivo. In intradermal Staphylococcus aureus infection that relies on inflammatory antigen transport, Arc/Arg3.1 deletion reduced T-cell responses. By contrast, Arc/Arg3.1 deficiency did not hamper the immune response to systemic Listeria monocytogenes infection, which does not require antigen transport. Thus, Arc/Arg3.1 expression is independent of ontogeny and phenotype and although it is restricted to a small fraction within each migDC subset and LCs, Arc/Arg3.1+ migDCs are important to facilitate infectious migration.


Asunto(s)
Movimiento Celular/genética , Proteínas del Citoesqueleto/genética , Células Dendríticas/inmunología , Células Dendríticas/metabolismo , Células de Langerhans/inmunología , Células de Langerhans/metabolismo , Proteínas del Tejido Nervioso/genética , Animales , Biomarcadores , Proteínas del Citoesqueleto/metabolismo , Modelos Animales de Enfermedad , Inmunofenotipificación , Inflamación/etiología , Inflamación/metabolismo , Ratones , Proteínas del Tejido Nervioso/metabolismo , Piel/inmunología , Piel/metabolismo , Piel/patología
2.
Sci Immunol ; 1(3): eaaf8665, 2016 Sep 23.
Artículo en Inglés | MEDLINE | ID: mdl-28783680

RESUMEN

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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