Lupus Nephritis: Immune Cells and The Kidney Microenvironment.

ABSTRACT

Lupus nephritis (LN) is the most common major organ manifestation of the autoimmune disease systemic lupus erythematosus (SLE, lupus), with 10% of those afflicted progressing to end-stage kidney disease. The kidney in LN is characterized by a significant immune infiltrate and proinflammatory cytokine milieu that affects intrinsic renal cells and is, in part, responsible for the tissue damage observed in LN. It is now increasingly appreciated that LN is not due to unidirectional immune cell activation with subsequent kidney damage. Rather, the kidney microenvironment influences the recruitment, survival, differentiation and activation of immune cells, which in turn modify kidney cell function. This review covers how the biochemical environment of the kidney (i.e. low oxygen tension and hypertonicity) and unique kidney cell types affect the intrarenal immune cells in LN. The pathways employed by intrinsic renal cells to interact with immune cells, such as antigen presentation and cytokine production, are discussed in detail. An understanding of these mechanisms can lead to the design of more kidney-targeted treatments and the avoidance of systemic immunosuppressive effects and may represent the next frontier of LN therapies.