Pathogenetic role of glomerular CXCL13 expression in lupus nephritis

Abstract

SummaryPodocytes maintain the structure and function of the glomerular filtration barrier. However, podocytes have recently been implicated in the innate immune response, and their function as non-haematopoietic antigenpresenting cells was highlighted. We have shown previously that excessive expression of the chemokine CXCL13 is a distinctive early event for nephritis in a murine model of systemic lupus erythematosus (SLE). Furthermore, we found that CXCL13 is elevated significantly in the serum of patients with SLE-nephritis. In this study, we were able to show for the first time that (i) CXCL13 is expressed locally in glomeruli in a model for SLE-nephritis in mice and that (ii) incubation of human podocytes with CXCL13 induces receptor stimulation of CXCR5 with activation of signalling pathways, resulting in (iii) secretion of proinflammatory cytokines and chemokines in culture supernatant. This cytokine/chemokine cocktail can lead to (iv) a neutrophil respiratory burst in isolated human granulocytes. Taken together, our results provide further evidence that CXCL13 is involved in the pathogenesis of glomerulonephritis and that podocytes can play an active role in local proinflammatory immune responses. Thus, CXCL13 could be a direct target for the therapy of glomerulonephritis in general and for SLE-nephritis in particular.

Molecular imaging of the kidney in lupus nephritis to characterize response to treatment

“…Transcripts for the B cell chemoattractant CXCL13, which is selective for B cells and follicular T cells were upregulated. CXCL13 has also previously been implicated in the pathogenesis of SLE in experimental models (17, 18), and serum levels correlated with SLE and LN disease activity (19). …”

CXCL13 as a new biomarker of systemic lupus erythematosus and lupus nephritis – from bench to bedside?

“…The podocyte activation resulted in secretion of proinflammatory cytokines and chemokines into the culture supernatant. This cytokine/chemokine cocktail was sufficient to induce a neutrophil respiratory burst in isolated human granulocytes, indicating that CXCL13 may have local proinflammatory effects [36]. Moreth and co-workers discovered a mechanism by which CXCL13 is induced.…”

CXCL13 Promotes Proliferation of Mesangial Cells by Combination with CXCR5 in SLE

“…Researchers found that it was correlated with disease activity and renal involvement. The pathogenetic role of CXCL13 in podocytes has been found by Worthmann et al [ 20 ]. However, there were few reports about the relationship between CXCL13 and mesangial cells.…”