FR-?~+Ly6C~+ Macrophages Could Serve As A Biomarker To Differentiate Liver Fibrosis Stage In SPECT Imaging

Although recruited macrophages play a central role in liver fibrogenesis,evidence has shown divergent roles of recruited macrophages in fibrosis progression and reversal.This might be mediated by functionally opposing subpopulations of Ly6C+(Grl+)macrophages.Folate receptor Beta(FR-?)has been found to be expressed on macrophages in arthritis and pneumonia.The expression of FR-? in liver fibrosis has not been reported,and the study on whether FR-? can be used as a marker of monocyte macrophages subpopulations has not been studied.Here we report that folate receptor-?(FR-?)expression identifies two functionally distinct subsets of hepatic Ly6C+ macrophages during liver fibrosis:FR-(3+Ly6C+ and FR-P-Ly6C+ cells.The FR-?+Ly6C+ subset plays a critical role in promoting hepatic fibrosis and initiating liver progenitor cell-mediated liver regeneration,whereas FR-?-Ly6C+ macrophages are associated with fibrosis resolution.They have a distinct pattern of cytokine expression.Furthermore,Hypoxia inducible factor-1 alpha(HIF-1?)activation in response to liver damage is critical for the regulation of FR-P expression and differentiation of two subsets of hepatic Ly6C+ macrophages.HIF-la can promote the expression of FR-?,increase the expression of TNF-? and TGF-1?.and promote the development of fibrosis.In addition,The expression of FR-? was closely correlated with the stage of liver fibrosis.With the characteristic of ASGPR,we explored SPECT imaging based on FR-? and ASGPR to differentiate liver fibrosis stage and quantify liver inflammation and fibrogenesis,which would be a novel target for hepatic fibrosis diagnosis and therapy.