PXD074605-1

PXD074605 is an original dataset announced via ProteomeXchange.

Title	Subversion of kynurenine-induced AHR activation in CD8 T cells by kynureninase-expressing antigen presenting cells
Description	Kynurenine, an intermediate metabolite of tryptophan metabolism, suppresses the antitumor activity of CD8+ T cells by activating the aryl hydrocarbon receptor (AHR). Its role in adaptive immunity is poorly understood. Outside the liver, kynurenine is mainly produced by indoleamine 2,3-dioxygenase 1 (IDO1) and further degraded by kynureninase (KYNU). This report shows that KYNU is predominantly expressed in human and mouse antigen-presenting cells (APCs) in vivo, GM-CSF-differentiated macrophages and dendritic cells in vitro, and alveolar macrophages collected in situ, and is functionally active in breaking down kynurenine into catabolic products without contributing towards de novo NAD+ synthesis. Importantly, while CD8+ T cells uptake kynurenine, they lack active KYNU, leading to AHR-dependent immunosuppression. However, KYNU-expressing APCs can deplete extracellular kynurenine, prevent AHR activation, and restore IFNγ production in CD8+ T cells. This highlights the importance of KYNU-expressing APCs in combating kynurenine-induced immune suppression against tumors.
HostingRepository	PRIDE
AnnounceDate	2026-02-23
AnnouncementXML	Submission_2026-02-23_07:34:16.753.xml
DigitalObjectIdentifier	https://dx.doi.org/10.6019/PXD074605
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Supported dataset by repository
PrimarySubmitter	J Patrick Murphy
SpeciesList	scientific name: Mus musculus (Mouse); NCBI TaxID: NEWT:10090;
ModificationList	TMT6plex-126 reporter+balance reagent acylated residue; iodoacetamide derivatized residue
Instrument	Orbitrap Fusion Lumos

Revision	Datetime	Status	ChangeLog Entry
0	2026-02-18 12:32:11	ID requested
⏵ 1	2026-02-23 07:34:17	announced

10.6019/PXD074605;

submitter keyword: Macrophages

J Patrick Murphy
contact affiliation	Department of Biology, University of Prince Edward Island
contact email	jpmurphy@upei.ca
lab head
J Patrick Murphy
contact affiliation	University of Prince Edward Island
contact email	jpmurphy@upei.ca
dataset submitter

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PRIDE project URI

• PRIDE
  1. PXD074605
     1. Label: PRIDE project
     2. Name: Subversion of kynurenine-induced AHR activation in CD8 T cells by kynureninase-expressing antigen presenting cells