کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
2831242 | 1570736 | 2011 | 8 صفحه PDF | دانلود رایگان |
![عکس صفحه اول مقاله: Blockade of TLR9 signaling in B cells impaired anti-dsDNA antibody production in mice induced by activated syngenic lymphocyte-derived DNA immunization Blockade of TLR9 signaling in B cells impaired anti-dsDNA antibody production in mice induced by activated syngenic lymphocyte-derived DNA immunization](/preview/png/2831242.png)
We previously established a systemic lupus erythematosus (SLE) animal model in non-susceptible BALB/c mice by immunizing with activated syngeneic lymphocyte-derived DNA (ALD-DNA), manifested by high level of anti-double-stranded DNA (dsDNA) antibodies (Abs), proteinuria, glomerular deposition of immune complex and glomerulonephritis. The production of anti-dsDNA Abs is closely related with the renal inflammation and damage in this model. However, recognition of ALD-DNA and its signaling pathway within antigen-presenting cells (APC) remains not fully clarified. Herein, in this study, Toll-like receptor 9 (TLR9), a well-known pattern-recognition receptor for dsDNA with CpG motif, was found to be dynamically up-regulated in B cells during the process of the SLE disease. Knockdown of TLR9 by short interfering RNA (siRNA) in B cells in vitro and in vivo reduced the production of anti-dsDNA antibody and consequently ameliorated the SLE syndrome in mice while the affinity and isotype of the antibody remained the same. Our results implied that TLR9 signaling of B cells might play an important role in the production of anti-dsDNA Abs triggered by auto dsDNA, which would extend our understanding of TLR9 immune recognition in the pathogenesis of SLE disease.
► TLR9 was dynamically up-regulated in B cells during the process of the SLE disease.
► The frequency of TLR9+ CD19+ B cells was correlated with the levels of anti-dsDNA Abs.
► Knockdown of TLR9 in B cells in vitro and in vivo impaired anti-dsDNA Ab production.
► Knockdown of TLR9 by siRNA in vivo ameliorated the SLE syndrome in lupus mice.
Journal: Molecular Immunology - Volume 48, Issues 12–13, July 2011, Pages 1532–1539