Differential induction of Ly6G and Ly6C positive myeloid derived suppressor cells in chronic kidney and liver inflammation and fibrosis

PLoS One. 2015 Mar 4;10(3):e0119662. doi: 10.1371/journal.pone.0119662. eCollection 2015.

Abstract

CD11b+Gr1+ myeloid derived suppressor cells (MDSC) are known to be very potent suppressors of T cell immunity and can be further stratified into granulocytic MDSC and monocytic MDSC in mice based on expression of Ly6G or Ly6C, respectively. Here, using these markers and functional assays, we aimed to identify whether MDSC are induced during chronic inflammation leading to fibrosis in both kidney and liver and whether additional markers could more specifically identify these MDSC subsets. In an adenine-induced model of kidney inflammation/fibrosis suppressive Ly6Gpos MDSC were induced. The suppressive function within the Ly6G+ MDSC population was exclusively present in IFNγRβ expressing cells. In contrast, in chronic inflammation in the liver induced by bile duct ligation, suppressive capacity was exclusively present in the Ly6Cpos MDSC subset. Gene expression analyses confirmed the differential origins and regulation of those MDSC subsets. Additionally, depletion of MDSC in either kidney or liver fibrosis enhanced fibrosis markers, indicating a protective role for MDSC in organ fibrosis. Thus, our data demonstrate that during liver inflammation and kidney fibrosis MDSC with similar function arise bearing a distinct marker profile and arising from different cell populations.

MeSH terms

  • Animals
  • Antigens, Ly / metabolism*
  • Biomarkers / metabolism
  • Disease Progression
  • Granulocytes / immunology
  • Granulocytes / metabolism
  • Inflammation / immunology
  • Liver Cirrhosis / immunology*
  • Mice
  • Myeloid Cells / immunology*
  • Myeloid Cells / metabolism*
  • Phenotype
  • Renal Insufficiency, Chronic / immunology*

Substances

  • Antigens, Ly
  • Biomarkers
  • Ly-6C antigen, mouse
  • Ly6G antigen, mouse

Grants and funding

LD was financially supported by a grant of the German research council (SFB704), BH by a BONFOR grant from the medical faculty of the university of Bonn, CK and ILP by SFB TRR57. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.