Editors' ChoiceImmunology

New connections: Making dendritic cells go faster

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Sci. Signal.  21 Nov 2017:
Vol. 10, Issue 506, eaar5246
DOI: 10.1126/scisignal.aar5246

Danger signals, such as microbial products or ATP, enhance the speed of migrating dendritic cells to lymph nodes to initiate an immune response.

Once dendritic cells (DCs) in peripheral tissues encounter danger-associated signals, such as the microbial product lipopolysaccharide (LPS) or ATP released from damaged cells, they migrate to lymph nodes to activate T cells and trigger an adaptive immune response. Two related studies have investigated the mechanisms by which danger signals increase the migratory speed of DCs. In Science Signaling, Sáez et al. showed that ATP stimulated P2X7 receptors in DCs, resulting in the opening of pannexin 1 (Panx1) channels and the release of ATP. This autocrine loop then increased their speed of migration. Compared to DCs from wild-type mice, DCs from Panx1-deficient mice migrated more slowly in vitro. When injected into the footpads of mice, ATP-treated Panx1-deficient DCs exhibited defective migration to draining lymph nodes. In Science Immunology, Bretou et al. showed that LPS treatment of DCs induced the release of calcium from lysosomes through the channel TRPML1. This resulted in the activation of the motor protein myosin II at the rear of the dendritic cell, promoting fast, directional migration. LPS-stimulated lysosomal calcium signaling also activated the transcription factor TFEB, which maintained the expression of TRPML1. Together, these data highlight mechanisms by which different dangers facilitate the fast migration of DCs to lymph nodes to initiate an adaptive immune response.

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