Tolksdorf, Felix, Mikulec, Julita, Geers, Bernd, Endig, Jessica, Sprezyna, Paulina, Heukamp, Lukas C., Knolle, Percy A. ORCID: 0000-0003-2983-0414, Kolanus, Waldemar and Diehl, Linda (2018). The PDL1-inducible GTPase Arl4d controls T effector function by limiting IL-2 production. Sci Rep, 8. LONDON: NATURE PUBLISHING GROUP. ISSN 2045-2322

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Abstract

Interleukin-2 (IL-2) is a key regulator of adaptive immune responses but its regulation is incompletely understood. We previously found that PDL1-dependent signals were pivotal for liver sinusoidal endothelial cell-mediated priming of CD8 T cells, which have a strongly reduced capacity to produce IL-2. Here, we show that the expression of the ARF-like GTPase Arl4d is PD-L1-dependently induced in such LSEC-primed T cells, and is associated with reduced IL-2 secretion and Akt phosphorylation. Conversely, Arl4d-deficient T cells overproduced IL-2 upon stimulation. Arl4d-deficiency in CD8 T cells also enhanced their expansion and effector function during viral infection in vivo. Consistent with their increased IL-2 production, Arl4d-deficient T cells showed enhanced development into KLRG1(+)CD127(-)short-lived effector cells (SLEC), which is dependent on IL-2 availability. Thus, our data reveal a PD-L1-dependent regulatory circuitry that involves the induction of Arl4d for limiting IL-2 production in T cells.

Item Type: Journal Article
Creators:
CreatorsEmailORCIDORCID Put Code
Tolksdorf, FelixUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Mikulec, JulitaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Geers, BerndUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Endig, JessicaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Sprezyna, PaulinaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Heukamp, Lukas C.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Knolle, Percy A.UNSPECIFIEDorcid.org/0000-0003-2983-0414UNSPECIFIED
Kolanus, WaldemarUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Diehl, LindaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
URN: urn:nbn:de:hbz:38-168892
DOI: 10.1038/s41598-018-34522-4
Journal or Publication Title: Sci Rep
Volume: 8
Date: 2018
Publisher: NATURE PUBLISHING GROUP
Place of Publication: LONDON
ISSN: 2045-2322
Language: English
Faculty: Unspecified
Divisions: Unspecified
Subjects: no entry
Uncontrolled Keywords:
KeywordsLanguage
SINUSOIDAL ENDOTHELIAL-CELLS; IN-VIVO; REGULATORY CELLS; AUTOCRINE IL-2; ACTIVATION; TOLERANCE; INTERLEUKIN-2; EXPANSION; RESPONSES; ANTIGENMultiple languages
Multidisciplinary SciencesMultiple languages
Refereed: Yes
URI: http://kups.ub.uni-koeln.de/id/eprint/16889

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