Plasmacytoid dendritic cell activation is dependent on coordinated expression 
of distinct amino acid transporters

Grzes, Katarzyna M; Sanin, David E; Kabat, Agnieszka M; Stanczak, Michal A; Edwards-Hicks, Joy; Matsushita, Mai; Hackl, Alexandra; Hässler, Fabian; Knoke, Kristin; Zahalka, Sophie; Villa, Matteo; Kofler, David M; Voll, Reinhard E; Zigrino, Paola; Fabri, Mario; Pearce, Erika Laine; Pearce, Edward Jonathen

doi:10.1016/j.immuni.2021.10.009

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Plasmacytoid dendritic cell activation is dependent on coordinated expression of distinct amino acid transporters

MPS-Authors

Grzes, Katarzyna M
Department Immunometabolism, Max Planck Institute of Immunobiology and Epigenetics, Max Planck Society;

Sanin, David E
Department Immunometabolism, Max Planck Institute of Immunobiology and Epigenetics, Max Planck Society;

Kabat, Agnieszka M
Department Immunometabolism, Max Planck Institute of Immunobiology and Epigenetics, Max Planck Society;

Stanczak, Michal A
Department Immunometabolism, Max Planck Institute of Immunobiology and Epigenetics, Max Planck Society;

Edwards-Hicks, Joy
Department Immunometabolism, Max Planck Institute of Immunobiology and Epigenetics, Max Planck Society;

Matsushita, Mai
Department Immunometabolism, Max Planck Institute of Immunobiology and Epigenetics, Max Planck Society;

Hackl, Alexandra
Department Immunometabolism, Max Planck Institute of Immunobiology and Epigenetics, Max Planck Society;

Hässler, Fabian
Department Immunometabolism, Max Planck Institute of Immunobiology and Epigenetics, Max Planck Society;

Villa, Matteo
Department Immunometabolism, Max Planck Institute of Immunobiology and Epigenetics, Max Planck Society;

/persons/resource/persons201431

Pearce, Erika Laine
Department Immunometabolism, Max Planck Institute of Immunobiology and Epigenetics, Max Planck Society;

/persons/resource/persons201435

Pearce, Edward Jonathen
Department Immunometabolism, Max Planck Institute of Immunobiology and Epigenetics, Max Planck Society;

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https://www.sciencedirect.com/science/article/pii/S1074761321004465?via%3Dihub
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Citation

Grzes, K. M., Sanin, D. E., Kabat, A. M., Stanczak, M. A., Edwards-Hicks, J., Matsushita, M., et al. (2021). Plasmacytoid dendritic cell activation is dependent on coordinated expression of distinct amino acid transporters. Immunity, 54, 2514-2530. doi:10.1016/j.immuni.2021.10.009.

Cite as: https://hdl.handle.net/21.11116/0000-000D-1787-1

Abstract

Human plasmacytoid dendritic cells (pDCs) are interleukin-3 (IL-3)-dependent cells implicated in autoimmunity, but the role of IL-3 in pDC biology is poorly understood. We found that IL-3-induced Janus kinase 2-dependent expression of SLC7A5 and SLC3A2, which comprise the large neutral amino acid transporter, was required for mammalian target of rapamycin complex 1 (mTORC1) nutrient sensor activation in response to toll-like receptor agonists. mTORC1 facilitated increased anabolic activity resulting in type I interferon, tumor necrosis factor, and chemokine production and the expression of the cystine transporter SLC7A11. Loss of function of these amino acid transporters synergistically blocked cytokine production by pDCs. Comparison of in vitro-activated pDCs with those from lupus nephritis lesions identified not only SLC7A5, SLC3A2, and SLC7A11 but also ectonucleotide pyrophosphatase-phosphodiesterase 2 (ENPP2) as components of a shared transcriptional signature, and ENPP2 inhibition also blocked cytokine production. Our data identify additional therapeutic targets for autoimmune diseases in which pDCs are implicated.