Physiological expression and function of the MDR1 transporter in cytotoxic T lymphocytes.
ATP Binding Cassette Transporter, Subfamily B, Member 1
/ genetics
Animals
Cell Survival
Core Binding Factor alpha Subunits
/ metabolism
Female
Gene Expression Regulation
Genetic Loci
Hematopoiesis
Mice, Inbred C57BL
Mitochondria
/ metabolism
Mitosis
Oxidative Stress
T-Lymphocytes, Cytotoxic
/ metabolism
Journal
The Journal of experimental medicine
ISSN: 1540-9538
Titre abrégé: J Exp Med
Pays: United States
ID NLM: 2985109R
Informations de publication
Date de publication:
04 05 2020
04 05 2020
Historique:
received:
27
07
2019
revised:
21
12
2019
accepted:
04
02
2020
entrez:
18
4
2020
pubmed:
18
4
2020
medline:
29
12
2020
Statut:
ppublish
Résumé
Multidrug resistance-1 (MDR1) acts as a chemotherapeutic drug efflux pump in tumor cells, although its physiological functions remain enigmatic. Using a recently developed MDR1-knockin reporter allele (Abcb1aAME), we found that constitutive MDR1 expression among hematopoietic cells was observed in cytolytic lymphocytes-including CD8+ cytotoxic T lymphocytes (CTLs) and natural killer cells-and regulated by Runt-related (Runx) transcription factors. Whereas MDR1 was dispensable for naive CD8+ T cell development, it was required for both the normal accumulation of effector CTLs following acute viral infection and the protective function of memory CTLs following challenge with an intracellular bacterium. MDR1 acted early after naive CD8+ T cell activation to suppress oxidative stress, enforce survival, and safeguard mitochondrial function in nascent CTLs. These data highlight an important endogenous function of MDR1 in cell-mediated immune responses and suggest that ongoing efforts to intentionally inhibit MDR1 in cancer patients could be counterproductive.
Identifiants
pubmed: 32302378
pii: 151682
doi: 10.1084/jem.20191388
pmc: PMC7201929
pii:
doi:
Substances chimiques
ATP Binding Cassette Transporter, Subfamily B, Member 1
0
Core Binding Factor alpha Subunits
0
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Subventions
Organisme : NCI NIH HHS
ID : T32 CA009161
Pays : United States
Organisme : NIAID NIH HHS
ID : U19 AI109976
Pays : United States
Organisme : NHLBI NIH HHS
ID : R01 HL125816
Pays : United States
Organisme : NIGMS NIH HHS
ID : T32 GM007308
Pays : United States
Organisme : NIAID NIH HHS
ID : R21 AI119728
Pays : United States
Organisme : NIAID NIH HHS
ID : R01 AI095634
Pays : United States
Organisme : NIAID NIH HHS
ID : R03 AI144714
Pays : United States
Informations de copyright
© 2020 Chen et al.
Déclaration de conflit d'intérêts
Disclosures: The authors declare no competing interests exist.
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