Expansion of myeloid-derived suppressor cells with aging in the bone marrow of mice through a NF-κB-dependent mechanism

Rafael R. Flores, Cheryl L. Clauson, Joonseok Cho, Byeong Chel Lee, Sara J. McGowan, Darren J. Baker, Laura J. Niedernhofer, Paul D. Robbins

Research output: Contribution to journalArticlepeer-review

27 Scopus citations

Abstract

With aging, there is progressive loss of tissue homeostasis and functional reserve, leading to an impaired response to stress and an increased risk of morbidity and mortality. A key mediator of the cellular response to damage and stress is the transcription factor NF-κB. We demonstrated previously that NF-κB transcriptional activity is upregulated in tissues from both natural aged mice and in a mouse model of a human progeroid syndrome caused by defective repair of DNA damage (ERCC1-deficient mice). We also demonstrated that genetic reduction in the level of the NF-κB subunit p65(RelA) in the Ercc1−/∆ progeroid mouse model of accelerated aging delayed the onset of age-related pathology including muscle wasting, osteoporosis, and intervertebral disk degeneration. Here, we report that the largest fraction of NF-κB -expressing cells in the bone marrow (BM) of aged (>2 year old) mice (C57BL/6-NF-κBEGFP reporter mice) are Gr-1+CD11b+myeloid-derived suppressor cells (MDSCs). There was a significant increase in the overall percentage of MDSC present in the BM of aged animals compared with young, a trend also observed in the spleen. However, the function of these cells appears not to be compromised in aged mice. A similar increase of MDSC was observed in BM of progeroid Ercc1−/∆ and BubR1H/H mice. The increase in MDSC in Ercc1−/∆ mice was abrogated by heterozygosity in the p65/RelA subunit of NF-κB. These results suggest that NF-κB activation with aging, at least in part, drives an increase in the percentage of MDSCs, a cell type able to suppress immune cell responses.

Original languageEnglish (US)
Pages (from-to)480-487
Number of pages8
JournalAging Cell
Volume16
Issue number3
DOIs
StatePublished - Jun 2017

Keywords

  • NF-κB
  • myeloid-derived suppressor cell
  • senescence

ASJC Scopus subject areas

  • Aging
  • Cell Biology

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