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 therapeuticsGrant support: ISCIII and FEDER funds CP14/00133, PI13/00047, Sociedad Española de Nefrologia, ISCIII-RETIC REDinREN/RD012/0021, Comunidad de Madrid CIFRA S2010/
BMD-2378. Salary support: FIS to LV-R, Miguel Servet to MS-N. Programa Intensificación Actividad Investigadora (ISCIII/
Agencia Laín-Entralgo/CM) to AO