The potential role of Th17 cells and Th17-related cytokines in the pathogenesis of lupus nephritis.
T helper type 17 (Th17) cells, a novel distinct subset of Th cell, can secrete interleukin (IL)-17 in humans. Although recent data suggest that Th17 cells and IL-17 play an important role in the pathogenesis of lupus nephritis (LN), the expression of Th17-related cytokines in the kidneys of SLE patients has not been studied in detail. In the present study, we investigated circulating Th17-cell frequencies using flow cytometry and serum Th17-related cytokine levels by enzyme-linked immunosorbent assay (ELISA) in 24 LN patients (17 patients with class IV and seven patients with class V) and 12 healthy controls. We also investigated glomerular Th17-related cytokine expression in LN patients and minimal change nephropathy (MCN) patients using immunohistochemistry. Our results showed significantly higher median frequencies of circulating Th17 cells in LN patients (0.68%) than in healthy controls (0.12%, p < 0.001). Serum levels of IL-17, IL-6 and IL-23 were significantly higher in LN patients (median 7.26, 232.60 and 37.01 pg/ml, respectively) than in healthy controls (median 0.82, 34.60 and 7.42 pg/ml, respectively; all p < 0.001). Circulating Th17-cell frequencies were positively correlated with SLEDAI, renal SLEDAI and histological activity index, the degree of cellular crescent and endocapillary proliferation. Significantly higher levels of glomerular IL-17 and IL-23 expression were observed in renal biopsies from class IV LN patients as compared to those from MCN patients and normal controls. Glomerular IL-17 and IL-23 expression levels were positively correlated with renal SLEDAI and histological activity index for LN patients. Our results suggest the potential role of the IL-23/Th17 axis in the intra-renal inflammation of SLE.
Division of Allergy, Immunology and Rheumatology, Taichung Veterans General Hospital and Faculty of Medicine, National Yang Ming University, Taiwan.
D-Y
DY
Chen
Y-M
YM
Chen
M-C
MC
Wen
T-Y
TY
Hsieh
W-T
WT
Hung
J-L
JL
Lan
D000328:Adult; D001706:Biopsy; D016022:Case-Control Studies; D016207:Cytokines / Q000097:blood*; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D005434:Flow Cytometry; D006801:Humans; D007150:Immunohistochemistry; D020381:Interleukin-17 / Q000097:blood; D020382:Interleukin-18 / Q000032:analysis; D053759:Interleukin-23 / Q000097:blood; D015850:Interleukin-6 / Q000097:blood; D007678:Kidney Glomerulus / Q000276:immunology* / Q000473:pathology; D008181:Lupus Nephritis / Q000097:blood / Q000276:immunology* / Q000473:pathology; D008297:Male; D008875:Middle Aged; D009402:Nephrosis, Lipoid / Q000276:immunology; D011379:Prognosis; D058504:Th17 Cells / Q000276:immunology*
D016207:Cytokines; C508600:IL6 protein, human; D020381:Interleukin-17; D020382:Interleukin-18; D053759:Interleukin-23; D015850:Interleukin-6