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Scientific article
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STIM1 promotes migration, phagosomal maturation and antigen cross-presentation in dendritic cells

Published inNature Communications, vol. 8, no. 1, 1852
Publication date2017
Abstract

Antigen cross-presentation by dendritic cells (DC) stimulates cytotoxic T cell activation to promote immunity to intracellular pathogens, viruses and cancer. Phagocytosed antigens generate potent T cell responses, but the signalling and trafficking pathways regulating their cross-presentation are unclear. Here, we show that ablation of the store-operated-Ca2+-entry regulator STIM1 in mouse myeloid cells impairs cross-presentation and DC migration in vivo and in vitro. Stim1 ablation reduces Ca2+ signals, cross-presentation, and chemotaxis in mouse bone-marrow-derived DCs without altering cell differentiation, maturation or phagocytic capacity. Phagosomal pH homoeostasis and ROS production are unaffected by STIM1 deficiency, but phagosomal proteolysis and leucyl aminopeptidase activity, IRAP recruitment, as well as fusion of phagosomes with endosomes and lysosomes are all impaired. These data suggest that STIM1-dependent Ca2+ signalling promotes the delivery of endolysosomal enzymes to phagosomes to enable efficient cross-presentation.

Keywords
  • Calcium signaling
  • Dendritic cells
  • Immunity
  • Phagocytosis
Citation (ISO format)
NUNES-HASLER, Paula et al. STIM1 promotes migration, phagosomal maturation and antigen cross-presentation in dendritic cells. In: Nature Communications, 2017, vol. 8, n° 1, p. 1852. doi: 10.1038/s41467-017-01600-6
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ISSN of the journal2041-1723
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