Intrarenal macrophage infiltration induced by T cells is associated with podocyte injury in lupus nephritis patients.

Abstract:

:Proteinuria is the hallmark of clinical manifestation of disease activity in lupus nephritis (LN) patients, which arises from direct or indirect podocyte injury. This study is to explore the relationship between intrarenal T cell infiltration and podocyte injury in lupus nephritis (LN), and to understand the potential mechanisms of podocyte injury induced by intrarenal T cells. Sixty renal biopsies from patients diagnosed with LN were included in the present study. Histological changes in LN patients were detected by light and electron microscopy. Podocyte-specific nephrin expression in renal tissues was detected by immunofluorescence. Infiltration of T cells (CD3+ cells), infiltration of macrophages (CD68+ cells) and the expression of osteopontin (OPN) in renal tissues were examined by immunohistochemical staining. Pearson or Spearman's tests were used to perform correlation analysis. Morphologic lesions of podocytes were more severe in LN patients than in normal control subjects. Compared with normal control subjects, nephrin expression was significantly decreased in LN patients. The expression level of nephrin was significantly lower in active LN patients than in the inactive group of patients (P < 0.05). Compared with normal control subjects, the number of infiltrated intrarenal T cells and macrophages was significantly increased in LN patients. T cells were mainly distributed in renal interstitium, with very few being in glomeruli, while macrophages were mainly located in glomeruli. The number of intrarenal infiltrated T cells and macrophages in active LN patients was more than that in the inactive group (P < 0.05). Compared with normal control subjects, OPN expression in LN patients was increased significantly. The expression level of OPN in active LN patients was significantly higher than that in the inactive group (P < 0.05). Podocyte-specific nephrin was negatively correlated with 24-hour proteinuria, intrarenal T cells infiltration and intrarenal OPN expression in LN patients (P < 0.001). Intrarenal macrophages had significantly positive correlation with intrarenal OPN expression (P < 0.001). The present study provides possible links between intrarenal T cells, OPN, macrophages with reduced podocyte-nephrin and podocytopathy in systemic lupus erythematosus. In addition, infiltration of macrophages in glomeruli induced by OPN that is induced by T cells may be a crucial mechanism for podocyte injury.

journal_name

Lupus

journal_title

Lupus

authors

Ma R,Jiang W,Li Z,Sun Y,Wei Z

doi

10.1177/0961203316646861

subject

Has Abstract

pub_date

2016-12-01 00:00:00

pages

1577-1586

issue

14

eissn

0961-2033

issn

1477-0962

pii

0961203316646861

journal_volume

25

pub_type

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