The Interplay of Chemokines and Dendritic Cells in the Pathogenesis of Lupus Nephritis

Abstract

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.

Lupus nephritis: current update

“…Second, DCs can migrate to local lymph nodes and potentially present renal autoantigens to T lymphocytes [58]. Third, since renal DCs express various co-stimulatory molecules such as CD40L, MHC II and chemokine receptors such as CCR1 and CCR5, they could directly interact with and activate intrinsic renal cells and other infiltrating inflammatory cells, hence perpetuating disease [58-60]. …”

Elevated interleukin-18 and skewed Th1:Th2 immune response in lupus nephritis

“…It has become evident that abnormal production of T helper (Th) cell cytokines [1][2][3][4] and chemokines [5] are primarily involved in kidney damage of SLE.…”

Effect of age on the immune system and pathology of mice with chronic graft-versus-host disease lupus nephritis

“…The severity of kidney disease in SLE patients is usually associated with anti-dsDNA antibody titer. Levels of autoantibodies and cytokines change during the development of LN (Gröndal et al, 2000;Reveille, 2004;Simón et al, 2004;Tucci et al, 2005;Kang and Datta, 2006;Moura et al, 2009). Patients' conditions may progress with age.…”