Universität zu Köln

Grzes, Katarzyna M., Sanin, David E., Kabat, Agnieszka M., Stanczak, Michal A., Edwards-Hicks, Joy ORCID: 0000-0002-9313-5718, Matsushita, Mai ORCID: 0000-0001-5693-461X, Hackl, Alexandra, Haessler, Fabian, Knoke, Kristin, Zahalka, Sophie, Villa, Matteo, Kofler, David M., Voll, Reinhard E., Zigrino, Paola, Fabri, Mario, Pearce, Erika L. and Pearce, Edward J. (2021). Plasmacytoid dendritic cell activation is dependent on coordinated expression of distinct amino acid transporters. Immunity, 54 (11). S. 2514 - 2539. CAMBRIDGE: CELL PRESS. ISSN 1097-4180

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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.

Item Type:	Journal Article
Creators:	Creators Email ORCID ORCID Put Code Grzes, Katarzyna M. UNSPECIFIED UNSPECIFIED UNSPECIFIED Sanin, David E. UNSPECIFIED UNSPECIFIED UNSPECIFIED Kabat, Agnieszka M. UNSPECIFIED UNSPECIFIED UNSPECIFIED Stanczak, Michal A. UNSPECIFIED UNSPECIFIED UNSPECIFIED Edwards-Hicks, Joy UNSPECIFIED orcid.org/0000-0002-9313-5718 UNSPECIFIED Matsushita, Mai UNSPECIFIED orcid.org/0000-0001-5693-461X UNSPECIFIED Hackl, Alexandra UNSPECIFIED UNSPECIFIED UNSPECIFIED Haessler, Fabian UNSPECIFIED UNSPECIFIED UNSPECIFIED Knoke, Kristin UNSPECIFIED UNSPECIFIED UNSPECIFIED Zahalka, Sophie UNSPECIFIED UNSPECIFIED UNSPECIFIED Villa, Matteo UNSPECIFIED UNSPECIFIED UNSPECIFIED Kofler, David M. UNSPECIFIED UNSPECIFIED UNSPECIFIED Voll, Reinhard E. UNSPECIFIED UNSPECIFIED UNSPECIFIED Zigrino, Paola UNSPECIFIED UNSPECIFIED UNSPECIFIED Fabri, Mario UNSPECIFIED UNSPECIFIED UNSPECIFIED Pearce, Erika L. UNSPECIFIED UNSPECIFIED UNSPECIFIED Pearce, Edward J. UNSPECIFIED UNSPECIFIED UNSPECIFIED
URN:	urn:nbn:de:hbz:38-595777
DOI:	10.1016/j.immuni.2021.10.009
Journal or Publication Title:	Immunity
Volume:	54
Number:	11
Page Range:	S. 2514 - 2539
Date:	2021
Publisher:	CELL PRESS
Place of Publication:	CAMBRIDGE
ISSN:	1097-4180
Language:	English
Faculty:	Unspecified
Divisions:	Unspecified
Subjects:	no entry
Uncontrolled Keywords:	Keywords Language SYSTEMIC-LUPUS-ERYTHEMATOSUS; INTERFERON-PRODUCING CELLS; COLONY-STIMULATING FACTOR; GM-CSF; INHIBITOR; GROWTH; METABOLISM; REVEALS; ALPHA; INTERLEUKIN-3 Multiple languages Immunology Multiple languages
URI:	http://kups.ub.uni-koeln.de/id/eprint/59577