Laser microdissection-based analysis of cytokine balance in the kidneys of patients with lupus nephritis.
To determine the cytokine balance in patients with lupus nephritis (LN), we analysed kidney-infiltrating T cells. Renal biopsy samples from 15 systemic lupus erythematosus (SLE) patients were used. In accordance with the classification of International Society of Nephrology/Renal Pathology Society, they were categorized into Class III, Class III+V (Class III-predominant group, n = 4), Class IV, Class IV+V (Class IV-predominant group, n = 7) and Class V (n = 4) groups. The single-cell samples of both the glomelular and interstitial infiltrating cells were captured by laser-microdissection. The glomerular and interstitial infiltrating T cells produced interleukin (IL)-2, IL-4, IL-10, IL-13 and IL-17 cytokines in the Class III-predominant, Class IV-predominant and Class V groups. Interferon-gamma was detected only in the glomeruli of the Class III-predominant and Class V group samples. The expression level of IL-17 was correlated closely with clinical parameters such as haematuria, blood urea nitrogen level, SLE Disease Activity Index scores in both glomeruli and interstitium, urine protein level in glomeruli and serum creatinine and creatinine clearance levels in interstitium. This suggests that the glomerular infiltrating T cells might act as T helper type 1 (Th1), Th2 and Th17 cells while the interstitial infiltrating T cells, act as Th2 and Th17 cells in the Class III-predominant and Class V groups. In contrast, both the glomerular and interstitial infiltrating T cells might act as Th2 and Th17 cells in the Class IV-predominant group. The cytokine balances may be dependent upon the classification of renal pathology, and IL-17 might play a critical role in SLE development.
Wang
Y
Y
Division of Clinical Immunology, Graduate School of Comprehensive Human Sciences, University of Tsukuba, Tennodai, Tsukuba, Japan.
Ito
S
S
Chino
Y
Y
Goto
D
D
Matsumoto
I
I
Murata
H
H
Tsutsumi
A
A
Hayashi
T
T
Uchida
K
K
Usui
J
J
Yamagata
K
K
Sumida
T
T
D000199:Actins / Q000235:genetics; D000293:Adolescent; D000328:Adult; D015415:Biomarkers / Q000097:blood / Q000652:urine; D001706:Biopsy; D016207:Cytokines / Q000235:genetics / Q000378:metabolism*; D005260:Female; D015870:Gene Expression / Q000235:genetics; D006801:Humans; D007371:Interferon-gamma / Q000378:metabolism; D020381:Interleukin-17 / Q000235:genetics; D007378:Interleukins / Q000378:metabolism; D007668:Kidney / Q000378:metabolism* / Q000473:pathology / Q000601:surgery; D007678:Kidney Glomerulus / Q000378:metabolism / Q000473:pathology; D053685:Laser Therapy; D008181:Lupus Nephritis / Q000276:immunology / Q000378:metabolism* / Q000473:pathology / Q000601:surgery; D008297:Male; D042282:Microdissection / Q000379:methods*; D008875:Middle Aged; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000235:genetics; D012720:Severity of Illness Index; D016176:T-Lymphocyte Subsets / Q000378:metabolism; D013601:T-Lymphocytes / Q000276:immunology / Q000378:metabolism*; D018417:Th1 Cells / Q000378:metabolism; D018418:Th2 Cells / Q000378:metabolism; D055815:Young Adult
D000199:Actins; D015415:Biomarkers; D016207:Cytokines; D020381:Interleukin-17; D007378:Interleukins; D016693:Receptors, Antigen, T-Cell, alpha-beta; D007371:Interferon-gamma