The interplay of chemokines and dendritic cells in the pathogenesis of lupus nephritis.
Lupus nephritis (LN) occurs in more that one-third of patients with systemic lupus erythematosus. Production of nephritogenic autoantibodies, glomerular immune complex deposition, and cytokine overproduction have been postulated to contribute to the pathogenesis of LN. However, overexpression of chemokines and imbalance of dendritic cell (DC) homeostasis may contribute to the development of nephritis in SLE. We present evidence that monocyte chemoattractant protein (MCP)-1 promotes renal disease in experimental glomerulonephritis, while its increased urinary levels reflect the severity of the disease in humans. Although macrophages are the prevalent infiltrating population within the kidney, it has been recently proposed that several chemokines and related receptors expressed by DCs may divide this cell population into myeloid (mDC) and plasmacytoid (pDC) subsets. However, the chemokine receptors expressed by pDCs are not functional, and other molecules are involved in the chemoattraction of these cells. We found increased expression of interleukin (IL)-18 in glomeruli of patients with active LN along with glomerular infiltration by pDCS. Since pDCs bear IL-18 receptor (IL-18R), it is conceivable that circulating pDCs may migrate toward glomeruli by IL-18/IL-18R interactions. Therefore, the relative depletion of circulating pDCs reflects the severity of inflammatory disease in LN.
Tucci
Marco
M
DIMO, University of Bari, Section of Internal Medicine and Oncology, Piazza Giulio Cesare 11, 70124 Bari, Italy.
Calvani
Nicola
N
Richards
Hanno B
HB
Quatraro
Cosima
C
Silvestris
Franco
F
D002465:Cell Movement; D018932:Chemokine CCL2 / Q000502:physiology; D018925:Chemokines / Q000502:physiology*; D003713:Dendritic Cells / Q000502:physiology*; D006801:Humans; D020382:Interleukin-18 / Q000502:physiology; D007668:Kidney / Q000473:pathology; D008181:Lupus Nephritis / Q000209:etiology*; D054390:Receptors, CCR2; D019707:Receptors, Chemokine / Q000502:physiology
C515334:CCR2 protein, human; D018932:Chemokine CCL2; D018925:Chemokines; D020382:Interleukin-18; D054390:Receptors, CCR2; D019707:Receptors, Chemokine