CXCL10 induces the recruitment of monocyte-derived macrophages into kidney, which aggravate puromycin aminonucleoside nephrosis

Abstract

SummaryThe mechanism responsible for trafficking of monocyte-derived macrophages into kidney in the puromycin aminonucleoside model of nephrotic syndrome in rats (PAN-NS), and the significance of this infiltration, remain largely unknown. CXCL10, a chemokine secreted in many T helper type 1 (Th1) inflammatory diseases, exhibits important roles in trafficking of monocytes and activated T cells. We hypothesized that induction of circulating interferon (IFN)-γ and glomerular tumour necrosis factor (TNF)-α during PAN-NS would stimulate the release of CXCL10 by podocytes, leading to infiltration of activated immune cells and greater glomerular injury. We found that serum IFN-γ, glomerular Cxcl10 mRNA and intra-and peri-glomerular macrophage infiltration were induced strongly during the late acute phase of PAN-NS in Wistar rats, but not in nude (Foxn1 rnu/rnu ) rats lacking functional effector T lymphocytes. Wistar rats also developed significantly greater proteinuria than nude rats, which could be abolished by macrophage depletion. Stimulation of cultured podocytes with both IFN-γ and TNF-α markedly induced the expression of Cxcl10 mRNA and CXCL10 secretion. Together, these data support our hypothesis that increased circulating IFN-γ and glomerular TNF-α induce synergistically the production and secretion of CXCL10 by podocytes, attracting activated macrophages into kidney tissue. The study also suggests that IFN-γ, secreted from Th1 lymphocytes, may prime proinflammatory macrophages that consequently aggravate renal injury.

Divergent roles for Ly6C+CCR2+CX3CR1+ inflammatory monocytes during primary or secondary infection of the skin with the intra-phagosomal pathogen Leishmania major

“…As expected we saw an early ifn γ response at 10h post-ch in LmLm but not NaLm mice (Fig 3I) and this was associated with increased levels of the chemokines cxcl10 and cxcl9 , both of which are induced by exposure to IFN-γ, and in the case of CXCL10, is involved in the recruitment of monocytes [27,28]. Peak cxcl10 expression occurred at 10h p.i., correlating with subsequent monocyte recruitment.…”

Mixed lineage kinase 3 mediates release of C‐X‐C motif ligand 10–bearing chemotactic extracellular vesicles from lipotoxic hepatocytes

“…CXCL10 has been extensively studied in hepatitis C as a hepatocyte‐derived chemotactic ligand and initiator of inflammatory cascades by its cognate receptor, (C‐X‐C motif) receptor 3 (CXCR3), which is widely expressed on Kupffer cells (the resident hepatic macrophages) and natural killer cells . CXCL10 is also known to attract activated monocyte‐derived macrophages in different models of tissue injury . Herein, we demonstrate that stimulation of BMDM with rmCXCL10‐ or CXCL10‐bearing EVs induce macrophage migration in a CXCL10‐dependent manner.…”

DDX3 Participates in Translational Control of Inflammation Induced by Infections and Injuries

“…CCL1 and CCL2, also called monocyte chemoattractant protein 1 (MCP1), are crucial for the recruitment of monocytes/macrophages to sites of inflammation (61). CCL5 and CXCL10 also participate in the recruitment of monocytes/macrophages in human adipose tissue and kidney (62,63). Therefore, we analyzed the effects of DDX3 knockdown on the recruitment of phagocytic cells.…”