Lupus nephritis (LN) is the most common major organ manifestation of the autoimmune disease SLE (lupus), with 10% of those afflicted progressing to ESKD. 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 used 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.