Universität zu Köln

Bopp, Luisa ORCID: 0000-0002-9089-5228, Martinez, Maria Lopéz, Schumacher, Clara ORCID: 0000-0003-0664-2023, Seitz, Robert ORCID: 0000-0003-0311-0777, Arana, Manuel Huerta ORCID: 0000-0003-3643-9077, Klapproth, Henning ORCID: 0000-0003-1966-3069, Lukas, Dominika ORCID: 0000-0002-9867-0891, Oh, Ju Hee, Neumayer, Daniela ORCID: 0000-0002-1333-8778, Lackmann, Jan W. ORCID: 0000-0001-8182-8034, Mueller, Stefan ORCID: 0000-0002-4861-3514, von Stebut, Esther ORCID: 0000-0001-9802-9642, Brachvogel, Bent ORCID: 0000-0002-3923-0554, Brodesser, Susanne ORCID: 0000-0001-5631-0663, Klein Geltink, Ramon I. and Fabri, Mario ORCID: 0000-0002-9586-2230 (2024). Glutamine promotes human CD8+ T cells and counteracts imiquimod-induced T cell hyporesponsiveness. iScience, 27 (5). pp. 1-20. Elsevier. ISSN 2589-0042

PDF 1-s2.0-S2589004224009891-main.pdf Bereitstellung unter der CC-Lizenz: Creative Commons Attribution Non-commercial. Download (3MB)

Abstract

[Artikel-Nr.: 109767] T cells protect tissues from cancer. Although investigations in mice showed that amino acids (AA) critically regulate T cell immunity, this remains poorly understood in humans. Here, we describe the AA composition of interstitial fluids in keratinocyte-derived skin cancers (KDSCs) and study the effect of AA on T cells using models of primary human cells and tissues. Gln contributed to ∼15% of interstitial AAs and promoted interferon gamma (IFN-γ), but not granzyme B (GzB) expression, in CD8+ T cells. Furthermore, the Toll-like receptor 7 agonist imiquimod (IMQ), a common treatment for KDSCs, down-regulated the metabolic gatekeepers c-MYC and mTORC1, as well as the AA transporter ASCT2 and intracellular Gln, Asn, Ala, and Asp in T cells. Reduced proliferation and IFN-γ expression, yet increased GzB, paralleled IMQ effects on AA. Finally, Gln was sufficient to promote IFN-γ-production in IMQ-treated T cells. Our findings indicate that Gln metabolism can be harnessed for treating KDSCs.

Item Type:	Article
Creators:	Creators Email ORCID ORCID Put Code Bopp, Luisa UNSPECIFIED https://orcid.org/0000-0002-9089-5228 UNSPECIFIED Martinez, Maria Lopéz UNSPECIFIED UNSPECIFIED UNSPECIFIED Schumacher, Clara UNSPECIFIED https://orcid.org/0000-0003-0664-2023 UNSPECIFIED Seitz, Robert UNSPECIFIED https://orcid.org/0000-0003-0311-0777 UNSPECIFIED Arana, Manuel Huerta UNSPECIFIED https://orcid.org/0000-0003-3643-9077 UNSPECIFIED Klapproth, Henning UNSPECIFIED https://orcid.org/0000-0003-1966-3069 UNSPECIFIED Lukas, Dominika UNSPECIFIED https://orcid.org/0000-0002-9867-0891 UNSPECIFIED Oh, Ju Hee UNSPECIFIED UNSPECIFIED UNSPECIFIED Neumayer, Daniela UNSPECIFIED https://orcid.org/0000-0002-1333-8778 UNSPECIFIED Lackmann, Jan W. UNSPECIFIED https://orcid.org/0000-0001-8182-8034 UNSPECIFIED Mueller, Stefan UNSPECIFIED https://orcid.org/0000-0002-4861-3514 UNSPECIFIED von Stebut, Esther UNSPECIFIED https://orcid.org/0000-0001-9802-9642 UNSPECIFIED Brachvogel, Bent UNSPECIFIED https://orcid.org/0000-0002-3923-0554 UNSPECIFIED Brodesser, Susanne UNSPECIFIED https://orcid.org/0000-0001-5631-0663 UNSPECIFIED Klein Geltink, Ramon I. UNSPECIFIED UNSPECIFIED UNSPECIFIED Fabri, Mario UNSPECIFIED https://orcid.org/0000-0002-9586-2230 UNSPECIFIED
URN:	urn:nbn:de:hbz:38-814204
Identification Number:	10.1016/j.isci.2024.109767
Journal or Publication Title:	iScience
Volume:	27
Number:	5
Page Range:	pp. 1-20
Number of Pages:	20
Date:	May 2024
Publisher:	Elsevier
ISSN:	2589-0042
Language:	English
Faculty:	Faculty of Mathematics and Natural Sciences Faculty of Medicine
Divisions:	CECAD - Cluster of Excellence Cellular Stress Responses in Aging-Associated Diseases Faculty of Medicine > Biochemie > Zentrum für Biochemie Faculty of Medicine > Dermatologie > Klinik und Poliklinik für Dermatologie und Venerologie Faculty of Medicine > Kinder- und Jugendmedizin > Klinik und Poliklinik für Kinder- und Jugendmedizin Zentrum für Molekulare Medizin
Subjects:	Medical sciences Medicine
['eprint_fieldname_oa_funders' not defined]:	Publikationsfonds UzK
Refereed:	Yes
URI:	http://kups.ub.uni-koeln.de/id/eprint/81420