Nrf2 is highly expressed in neutrophils, but myeloid cell-derived Nrf2 is dispensable for wound healing in mice

PloS One
Natasha Joshi, Sabine Werner

Abstract

Immune cells of the myeloid lineage are key players in skin wound healing, since they secrete various cytokines and growth factors that orchestrate the repair process. In addition, they are crucial for the defense against invading pathogens through their capacity to produce high levels of reactive oxygen species (ROS). To limit the toxicity of ROS, cells have developed antioxidant defense strategies, including expression of the cytoprotective NRF2 transcription factor. Here we show that murine neutrophils and to a lesser extent macrophages strongly express Nrf2 already when present in the circulation and in particular at the wound site. To determine the role of Nrf2 in neutrophils and macrophages for wound repair, we generated mice with a gain- or loss-of-function of this transcription factor in the myeloid cell lineage. Expression of a constitutively active Nrf2 mutant in myeloid cells did not further enhance the overall Nrf2 activity in these cells due to the already high steady-state activity of endogenous Nrf2. Surprisingly, deletion of Nrf2 in myeloid cells only mildly affected the levels of ROS and the expression of pro-inflammatory cytokines by these cells. In particular, various parameters of wound healing, including wo...Continue Reading

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Citations

Aug 17, 2019·PloS One·Doumet Georges HelouSylvie Chollet-Martin
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Methods Mentioned

BETA
ubiquitination
biopsy
fluorescence-activated cell sorting
flow cytometry
biopsies
fluorescence activated cell sorting
FACS
electrophoresis
transgenic

Software Mentioned

FIJI
FACSDiva TM
FlowJo
PRISM
BD FACSDiva TM
Graph pad

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