Universität zu Köln

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:	Creators Email ORCID ORCID Put Code Tolksdorf, Felix UNSPECIFIED UNSPECIFIED UNSPECIFIED Mikulec, Julita UNSPECIFIED UNSPECIFIED UNSPECIFIED Geers, Bernd UNSPECIFIED UNSPECIFIED UNSPECIFIED Endig, Jessica UNSPECIFIED UNSPECIFIED UNSPECIFIED Sprezyna, Paulina UNSPECIFIED UNSPECIFIED UNSPECIFIED Heukamp, Lukas C. UNSPECIFIED UNSPECIFIED UNSPECIFIED Knolle, Percy A. UNSPECIFIED orcid.org/0000-0003-2983-0414 UNSPECIFIED Kolanus, Waldemar UNSPECIFIED UNSPECIFIED UNSPECIFIED Diehl, Linda UNSPECIFIED UNSPECIFIED UNSPECIFIED
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:	Keywords Language SINUSOIDAL ENDOTHELIAL-CELLS; IN-VIVO; REGULATORY CELLS; AUTOCRINE IL-2; ACTIVATION; TOLERANCE; INTERLEUKIN-2; EXPANSION; RESPONSES; ANTIGEN Multiple languages Multidisciplinary Sciences Multiple languages
Refereed:	Yes
URI:	http://kups.ub.uni-koeln.de/id/eprint/16889