Physiological expression and function of the MDR1 transporter in cytotoxic T lymphocytes

被引：33

作者：

Chen, Mei Lan ^{[1
]}

Sun, Amy ^{[2
]}

Cao, Wei ^{[1
]}

Eliason, Amber ^{[1
]}

Mendez, Kayla M. ^{[1
]}

Getzler, Adam J. ^{[1
]}

Tsuda, Shanel ^{[1
]}

Diao, Huitian ^{[1
]}

Mukori, Clever ^{[1
]}

Bruno, Nelson E. ^{[3
]}

Kim, Sang Yong ^{[4
]}

Pipkin, Matthew E. ^{[1
]}

Koralov, Sergei B. ^{[2
]}

Sundrud, Mark S. ^{[1
]}

机构：

[1] Scripps Res Inst, Dept Immunol & Microbiol, Jupiter, FL 33458 USA

[2] NYU, Sch Med, Dept Pathol, New York, NY 10003 USA

[3] Scripps Res Inst, Dept Integrat Struct & Computat Biol, Jupiter, FL USA

[4] NYU, Rodent Genet Engn Core, Med Ctr, New York, NY 10016 USA

来源：

JOURNAL OF EXPERIMENTAL MEDICINE | 2020年 / 217卷 / 05期

基金：

美国国家卫生研究院;

关键词：

PRODUCT P-GLYCOPROTEIN; MULTIDRUG-RESISTANCE; CHROMATIN ACCESSIBILITY; TISSUE DISTRIBUTION; EFFLUX PUMP; CELL-DEATH; PHASE-I; GENE; RUNX3; PHARMACOKINETICS;

D O I：

10.1084/jem.20191388

中图分类号：

R392 [医学免疫学]; Q939.91 [免疫学];

学科分类号：

100102 ;

摘要：

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 (Abcb1a(AM)(E)), 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.

引用

页数：18

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