Background/Purpose: Macrophages and dendritic cells contribute to renal damage in chronic renal diseases including lupus nephritis. However owing to their multiple phenotypic and functional variations, the role of these cells in organ pathology is still not defined.  The present work examines the phenotype and functional characteristics of renal macrophages and dendritic cells in two murine lupus nephritis models.

Methods: A bead based enrichment step followed by cell sorting was used to isolate populations of interest. Cells were cultured in M-CSF or GM-CSF +/- LPS/IFN¥ and analyzed by microscopy and for arginase activity and nitrite production. Antigen presentation capability was measured in mixed lymphocyte reactions. Flow cytometry was performed using multiple phenotypic markers. Gene expression was performed using real-time PCR.

Results: We identified two populations of macrophages and three populations of dendritic cells in both SLE models, with a large increase in the number of cells belonging to two of these five populations during active nephritis. F4/80^hi monocyte derived macrophages, that are normally resident in the kidneys and increase in number during nephritis, do not differentiate into either M1 or M2 macrophages upon cytokine stimulation and acquire a mixed pro and anti-inflammatory functional phenotype during nephritis in both SLE strains that resembles the constitutively activated phenotype of gut F4/80^hi macrophages. F4/80^lo macrophages are infrequent in the kidneys of both strains and do not alter their phenotype during nephritis. CD11c^hi/CD103^– DCs accumulate in large numbers during nephritis. These cells have a myeloid DC phenotype and can easily be distinguished from resident renal CD103+ DCs on the basis of morphology, motility and cell surface phenotype. Patterns of TLR expression and chemokine receptors differ between subsets.

Conclusion:  This study highlights the heterogeneity of the macrophage/DC infiltrate in chronic SLE nephritis and provides an initial phenotypic and functional analysis of the different cellular components that can now be used to define the role of each subset in nephritis progression or amelioration.

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ACR Meeting Abstracts - https://acrabstracts.org/abstract/characterization-of-renal-mononuclear-phagocyte-populations-in-murine-sle-nephritis/