Role of pathogenic auto-antibody production by Toll-like receptor 9 of B cells in active systemic lupus erythematosus.
OBJECTIVE
Toll-like receptor 9 (TLR9) is a pattern-associated receptor functioning in innate immunity that may be involved in the recognition of self-antigens and the production of pathogenic auto-antibodies. Therefore, we examined the expression of TLR9 in systemic lupus erythematosus (SLE) to determine whether TLR9 is involved in the production of pathogenic auto-antibodies.


METHODS
B cells were collected from patients with active SLE, and subjected to analysis of the TLR9 molecule using flow cytometry fluorescence activated cell sorting (FACS) and TLR9 mRNA by reverse-transcriptase polymerase chain reaction. SLE B cells were stimulated with CpG-ODN, and subsequent cytokine and anti-dsDNA antibody production was measured by enzyme-linked immunosorbent assay.


RESULTS
The expression and mRNA level of TLR9 on B cells was up-regulated in SLE patients, and SLE disease activity index (SLEDAI) and CH50 were correlated with TLR9 expression on CD20+ B cells. Moreover, TLR9-CpG interaction enhanced the production of anti-dsDNA antibody and IL-10.


CONCLUSIONS
The present study demonstrated that higher expression of TLR9 on peripheral blood B cells from patients with active SLE was significantly correlated with CH50 and SLEDAI to TLR9, and induced the production of anti-dsDNA antibody and IL-10 by TLR9-CpG ligation. These results suggest that an abnormality of innate immunity plays a crucial role in the pathology of SLE, and that blockade of CpG-TLR9 interaction may be a new therapeutic approach for SLE.
Nakano
S
S
Department of Rheumatology and Internal Medicine, Juntendo University School of Medicine, 2-1-1 Hongo, Bunkyo-Ku, Tokyo 113-8421, Japan. soubey@med.juntendo.ac.jp
Morimoto
S
S
Suzuki
J
J
Nozawa
K
K
Amano
H
H
Tokano
Y
Y
Takasaki
Y
Y
D000293:Adolescent; D000328:Adult; D001172:Arthritis, Rheumatoid / Q000235:genetics / Q000276:immunology; D001323:Autoantibodies / Q000235:genetics / Q000276:immunology*; D001402:B-Lymphocytes / Q000276:immunology*; D018899:CpG Islands / Q000276:immunology; D005260:Female; D005434:Flow Cytometry; D005786:Gene Expression Regulation / Q000276:immunology; D006801:Humans; D008180:Lupus Erythematosus, Systemic / Q000276:immunology*; D008297:Male; D008875:Middle Aged; D012333:RNA, Messenger / Q000235:genetics; D012016:Reference Values; D051217:Toll-Like Receptor 9 / Q000235:genetics* / Q000276:immunology*
D001323:Autoantibodies; D012333:RNA, Messenger; D051217:Toll-Like Receptor 9