Impact of Particulate Matter on the Exacerbation of Immunoglobulin A Nephropathy: An Animal Experimental Study

TL;DR

This study shows that exposure to particulate matter worsens immunoglobulin A nephropathy in mice through immune system activation.

Contribution

The study experimentally demonstrates that PM exposure exacerbates IgAN via TLR9-mediated immune activation and aberrant IgA glycosylation.

Findings

PM exposure increased lung TLR9 expression and was associated with pigment-laden macrophages.

HIGA mice exposed to PM showed elevated aberrant IgA and APRIL levels with worsened kidney pathology.

Transcriptomic analysis revealed immune dysregulation in splenic B cells of PM-exposed HIGA mice.

Abstract

Particulate matter (PM) exposure is linked to chronic kidney disease; however, its effect on immunoglobulin A (IgA) nephropathy (IgAN) remains unclear. We investigated whether PM exposure exacerbates IgAN in a mouse model. HIGA mice (IgAN model) and BALB/c controls were exposed to PM in a sealed chamber for 13 weeks. Lung Toll-like receptor 9 (TLR9) expression, serum aberrantly glycosylated IgA, A proliferation-inducing ligand (APRIL) levels, mesangial IgA deposition, and kidney pathology were assessed. RNA sequencing of splenic B cells was performed to evaluate immune-related gene expression. PM exposure increased lung TLR9 expression in both strains, particularly around pigment-laden macrophages. HIGA mice showed elevated aberrant IgA and APRIL levels, with aggravated mesangial expansion and IgA deposition. Transcriptomic analysis revealed immune dysregulation in splenic B cells of PM-exposed HIGA mice. Our findings provide experimental evidence that PM exposure aggravates IgAN via TLR9-mediated mucosal immune activation, leading to aberrant IgA glycosylation and mesangial deposition. These findings emphasize that reducing PM exposure may benefit patients with IgAN.

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