Differential induction of Ly6G and Ly6C positive myeloid derived suppressor cells in chronic kidney and liver inflammation and fibrosis.
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.
Institute for Molecular Medicine, University of Bonn, Bonn, Germany; Institute of Molecular Immunology, Technische Universität München, Munich, Germany.
Bastian
B
Höchst
Institute for Molecular Medicine, University of Bonn, Bonn, Germany.
Julita
J
Mikulec
Institute for Experimental Immunology, University of Bonn, Bonn, Germany.
Tania
T
Baccega
Institute for Molecular Medicine, University of Bonn, Bonn, Germany.
Christina
C
Metzger
Institute for Molecular Medicine, University of Bonn, Bonn, Germany.
Meike
M
Welz
Department of Medicine III, University Hospital Aachen, Aachen, Germany.
Julia
J
Peusquens
Department of Medicine III, University Hospital Aachen, Aachen, Germany.
Frank
F
Tacke
Institute for Molecular Medicine, University of Bonn, Bonn, Germany; Institute of Molecular Immunology, Technische Universität München, Munich, Germany.
Percy
P
Knolle
Institute for Experimental Immunology, University of Bonn, Bonn, Germany.
Christian
C
Kurts
Institute for Molecular Medicine, University of Bonn, Bonn, Germany; Institute of Experimental Immunology and Hepatology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.
Linda
L
Diehl
Institute for Experimental Immunology, University of Bonn, Bonn, Germany.
Isis
I
Ludwig-Portugall
D000818:Animals; D000950:Antigens, Ly / Q000378:metabolism*; D015415:Biomarkers / Q000378:metabolism; D018450:Disease Progression; D006098:Granulocytes / Q000276:immunology / Q000378:metabolism; D007249:Inflammation / Q000276:immunology; D008103:Liver Cirrhosis / Q000276:immunology*; D051379:Mice; D022423:Myeloid Cells / Q000276:immunology* / Q000378:metabolism*; D010641:Phenotype; D051436:Renal Insufficiency, Chronic / Q000276:immunology*
D000950:Antigens, Ly; D015415:Biomarkers; C494192:Ly-6C antigen, mouse; C480309:Ly6G antigen, mouse