Mapping urinary chemokines in human lupus nephritis: Potentially redundant pathways recruit CD4+ and CD8+ T cells and macrophages

Renal infiltration of inflammatory cells contributes to the pathogenesis of lupus nephritis (LN). Current knowledge on the recruitment mechanisms relies mainly on findings in rodent models. Here, we assess various chemokine pathways in human LN by comparing urinary chemokine concentrations (in 25 patients with acute LN and in 78 lupus patients without active LN) with the expression of corresponding chemokine receptors on urinary leukocytes (in ten acute LN patients). Nine urinary chemokineswere significantly elevated in LN patients and correlated with renal disease activity and urinary cell counts; however, their concentrations displayed considerable interindividual heterogeneity. Analysis of the corresponding receptors revealed abundance of urinary CD8(+) T cells for CCR5 and CXCR3, while CD4(+) T cells were additionally enriched for CCR1, CCR6 and CXCR6. Urinary Treg showed similar CCR expression, and urinary CD14(+) macrophages were enriched for CCR5 expressing cells. In conclusion, cell specific recruitment patterns seem to involve CCR5 and CXCR3 in all cells studied, while CD4(+) T-cell subset recruitment is probably much more varied. However, urinary chemokine abundance in active LN is individually variable in our cohort and does not offer a singular chemokine usable as universal biomarker or potential future treatment target.