Multidrug resistance (MDR)-1 acts as a chemotherapeutic drug efflux pump in tumor cells, although its physiologic functions remain enigmatic. Using a recently-developed MDR1-knockin reporter allele (Abcb1aAME/+), we found that constitutive MDR1 expression amongst hematopoietic cells was observed mainly in cytolytic lymphocytesincluding CD8+ cytotoxic T lymphocytes (CTL) and natural killer cellsand regulated by Runt-related (Runx) transcription factors. Although MDR1 was dispensable for nave CD8+ T cell development, it was required for both normal accumulation of effector CTL following acute viral infection and protective function of memory CTL upon challenge with an intracellular bacterium. MDR1 acted early after nave CD8+ T cell activation to suppress oxidative stress, enforce survival and safeguard mitochondrial function in developing CTL. Together, 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 counter-productive. SOURCE: Mark Sundrud (msundrud@scripps.edu, meichen@scripps.edu) - Sundrud Lab The Scripps Research Institute

Pluto Bioinformatics

GSE143139: RNA-Seq of Day 6 in vitro generated cells with and without Mdr1 expression and Elacridar treatment