Expression of Toll-like receptor 9 in renal podocytes in childhood-onset active and inactive lupus nephritis.
BACKGROUND
Childhood-onset systemic lupus erythematosus (SLE) is frequently complicated with lupus nephritis (LN), which is characterized by the deposition of DNA-containing immune complex to the glomerulus. Toll-like receptor 9 (TLR9), capable of recognizing the microbially derived CpG oligonucleotide, plays a crucial role in the innate immunity. TLR9 is also assumed to be related to the aetiology of SLE in the recognition of anti-DNA antibody-containing immune complex, but this remains controversial. We conducted a study to elucidate the association between TLR9 and LN in childhood-onset SLE.


METHODS
We compared the expression and localization of TLR9 and the slit membrane-related protein in the biopsied kidney sample by immunostaining in four children with active or inactive LN. We also evaluated their laboratory findings, such as anti-DNA antibody, complement and proteinuria at biopsy, to assess the correlation to the findings of the immunostaining.


RESULTS
TLR9 is not expressed in a normal control kidney. However, TLR9 develops in podocytes only in active LN but disappears in remission. Meanwhile, the slit membrane-related proteins such as nephrin, podocin and synaptopodin in podocytes express clearly and uniformly in remission, but their expression is markedly diminished in active LN, which results in podocyte injury. When TLR9 is expressed in podocytes, all the patients simultaneously showed hypocomplementaemia, high titre of anti-double-stranded DNA (dsDNA) antibody and proteinuria.


CONCLUSIONS
Injured podocytes in active LN express TLR9. This expression could be associated with proteinuria and increased anti-dsDNA antibody. This is the first report indicating that TLR9 is involved in the aetiology of LN and that it may play some role in podocyte injury.
Machida
Hiroyuki
H
Department of Pediatrics, Yokohama City University, Japan. helmet@nyc.odn.ne.jp
Ito
Shuichi
S
Hirose
Tomonori
T
Takeshita
Fumihiko
F
Oshiro
Hisashi
H
Nakamura
Tomoko
T
Mori
Masaaki
M
Inayama
Yoshiaki
Y
Yan
Kunimasa
K
Kobayashi
Naoto
N
Yokota
Shumpei
S
D000293:Adolescent; D000888:Antibodies, Anti-Idiotypic / Q000097:blood; D001706:Biopsy; D002648:Child; D004247:DNA / Q000276:immunology; D005260:Female; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins / Q000378:metabolism; D007668:Kidney / Q000378:metabolism / Q000473:pathology; D008180:Lupus Erythematosus, Systemic / Q000150:complications*; D008181:Lupus Nephritis / Q000209:etiology* / Q000378:metabolism*; D008297:Male; D008565:Membrane Proteins / Q000378:metabolism; D008840:Microfilament Proteins / Q000378:metabolism; D050199:Podocytes / Q000378:metabolism* / Q000473:pathology; D051217:Toll-Like Receptor 9 / Q000378:metabolism*
D000888:Antibodies, Anti-Idiotypic; D047908:Intracellular Signaling Peptides and Proteins; D008565:Membrane Proteins; D008840:Microfilament Proteins; C407223:NPHS2 protein; C503967:SYNPO protein, human; C495371:TLR9 protein, human; D051217:Toll-Like Receptor 9; C113267:nephrin; D004247:DNA