CD74 in Kidney Disease

Abstract

CD74 (invariant MHC class II) regulates protein trafficking and is a receptor for macrophage migration inhibitory factor (MIF) and d-dopachrome tautomerase (d-DT/MIF-2). CD74 expression is increased in tubular cells and/or glomerular podocytes and parietal cells in human metabolic nephropathies, polycystic kidney disease, graft rejection and kidney cancer and in experimental diabetic nephropathy and glomerulonephritis. Stressors like abnormal metabolite (glucose, lyso-Gb3) levels and inflammatory cytokines increase kidney cell CD74. MIF activates CD74 to increase inflammatory cytokines in podocytes and tubular cells and proliferation in glomerular parietal epithelial cells and cyst cells. MIF overexpression promotes while MIF targeting protects from experimental glomerular injury and kidney cysts, and interference with MIF/CD74 signaling or CD74 deficiency protected from crescentic glomerulonephritis. However, CD74 may protect from interstitial kidney fibrosis. Furthermore, CD74 expression by stressed kidney cells raises questions about the kidney safety of cancer therapy strategies delivering lethal immunoconjugates to CD74-expressing cells. Thus, understanding CD74 biology in kidney cells is relevant for kidney therapeutics.

Macrophage Migration Inhibitory Factor Induces Inflammation and Predicts Spinal Progression in Ankylosing Spondylitis

“…Co-receptors such as CXCR2, CXCR4, and CD44 (40) have been reported to be involved in transducing MIF signals along with CD74. Co-receptors such as CXCR2, CXCR4, and CD44 (40) have been reported to be involved in transducing MIF signals along with CD74.…”

Up-Regulation of CD74 Expression in Parietal Epithelial Cells in a Mouse Model of Focal Segmental Glomerulosclerosis

“…CD74 is known to be the cell surface form of the MHC class II invariant chain and works as a cell membrane receptor for MIF, forming a complex with CD44 [9,11,12]. By immunohistochemistry, CD74 staining was observed to be co-localized with CD44 in some epithelial cells lining the BC in ADR-injured glomeruli, suggesting a role for CD74 expression in PEC activation.…”

“…CD44 is also known to interact with CD74, major histocompatibility complex (MHC) class II invariant chain [9]. CD74 acts as a cell membrane receptor for the macrophage migration inhibitory factor (MIF), and the formation of the CD44-CD74 complex initiates the signaling pathway triggered by MIF in macrophages [9] and B cells [10,11,12], inducing cell proliferation and survival. Moreover, several studies suggested a role for CD74 expression in the progression of thyroid, breast, pancreatic, skin and gastrointestinal tract cancers [13,14,15,16]; however, only a few studies were conducted to evaluate the role of CD74 expression and that of CD74-CD44 complex in kidney diseases [17,18].…”

Mapping of human B-cell epitopes of Sindbis virus

“…In general, CD74 functions as a chaperone by blocking unwanted peptide binding to MCH type II, but approximately 5 % of the CD74 population is found on the cell surface, where CD74 serves as a receptor for MIF (Stumptner-Cuvelette & Benaroch, 2002;Wraight et al, 1990). MIF has been linked to many diseases with an inflammatory component, including atherosclerosis, kidney diseases and rheumatoid arthritis (Bernhagen et al, 2007;Morand & Leech, 2005;Valiño-Rivas et al, 2015). MIF has also been shown to increase leucocyte proliferation, chemotaxis and survival as well as the production of inflammatory cytokines, and antibodies (Bacher et al, 1996;Bernhagen et al, 2007;Gore et al, 2008;Marsh et al, 2009;Starlets et al, 2006).…”