Differential Induction of Ly6G and Ly6C Positive Myeloid Derived Suppressor Cells in Chronic Kidney and Liver Inflammation and Fibrosis

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.

Phenotypically resembling myeloid derived suppressor cells are increased in children with HIV and exposed/infected with Mycobacterium tuberculosis

“…We also assessed peripheral frequencies of M‐MDSCs and G‐MDSCs, as subset‐specific differences have been observed in several disease conditions . Our findings indicate that cells representing the M‐MDSC subset, is the predominant phenotype in PBMCs amongst all study groups.…”

S100A8/A9 promotes parenchymal damage and renal fibrosis in obstructive nephropathy

“…Although we detected S100A8/A9 expression mainly on infiltrating granulocytes, mice lacking S100A9 displayed similar granulocyte numbers compared to WT mice, as shown previously by our group in the acute model of injury , suggesting a limited role of S100A8/A9 in granulocyte infiltration in both acute and chronic models of renal injury. Nonetheless, the role of granulocytes in the progression of renal fibrosis is not as pronounced as the role of macrophages . Instead, the latter play a pivotal role in the development of tubulo‐interstitial injury, due to the activation of an excessive inflammatory response .…”

Characterization of Liver Monocytic Myeloid-Derived Suppressor Cells and Their Role in a Murine Model of Non-Alcoholic Fatty Liver Disease

“…Recently, MDSCs have been found to accumulate in the livers of obese mice to suppress inflammation and maintain liver homeostasis; these MDSCs were identified as CD11b + Gr1 + [ 14 , 15 ]. The Gr1 marker is a composite epitope between Ly6C and Ly6G antigens, and MDSCs can be further subdivided into Ly6C + monocytic and Ly6G + granulocytic MDSCs using these 2 antigens [ 12 , 16 ]. However, other studies have reported that liver CD11b + Ly6C + or CD11b + Gr1 + cells, categorized as macrophages, monocytes, or immature myeloid cells, contribute to liver inflammation [ 17 – 19 ], suggesting that the phenotype of liver MDSCs needs further investigation and specification.…”