TACI deletion protects against progressive murine lupus nephritis induced by BAFF overexpression.
TACI deletion protects against progressive murine lupus nephritis induced by BAFF overexpression.
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DOI：
10.1016/j.kint.2018.03.012
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发表时间：
2018-10
影响因子：
19.6
通讯作者：
Jackson SW
中科院分区：
文献类型：
--
作者：
Arkatkar T;Jacobs HM;Du SW;Li QZ;Hudkins KL;Alpers CE;Rawlings DJ;Jackson SW
B cells are known to promote the pathogenesis of systemic lupus erythematosus (SLE) via the production of pathogenic anti-nuclear antibodies. However, the signals required for autoreactive B cell activation and the immune mechanisms whereby B cells impact lupus nephritis pathology remain poorly understood. The B cell survival cytokine B cell activating factor of the TNF Family (BAFF) has been implicated in the pathogenesis of SLE and lupus nephritis in both animal models and human clinical studies. Although the BAFF receptor has been predicted to be the primary BAFF family receptor responsible for BAFF-driven humoral autoimmunity, in the current study we identify a critical role for signals downstream of Transmembrane Activator and CAML Interactor (TACI) in BAFF-dependent lupus nephritis. Whereas transgenic mice overexpressing BAFF develop progressive membranoproliferative glomerulonephritis, albuminuria and renal dysfunction, TACI deletion in BAFF-transgenic mice provided long-term (about 1 year) protection from renal disease. Surprisingly, disease protection in this context was not explained by complete loss of glomerular immune complex deposits. Rather, TACI deletion specifically reduced endocapillary, but not mesangial, immune deposits. Notably, although excess BAFF promoted widespread breaks in B cell tolerance, BAFF-transgenic antibodies were enriched for RNA- relative to DNA-associated autoantigen reactivity. These RNA-associated autoantibody specificities were specifically reduced by TACI or Toll-like receptor 7 deletion. Thus, our study provides important insights into the autoantibody specificities driving proliferative lupus nephritis, and suggests that TACI inhibition may be novel and effective treatment strategy in lupus nephritis.
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DOI：
10.4049/jimmunol.1400098
发表时间：
2014-05-15
期刊：
Journal of immunology (Baltimore, Md. : 1950)
影响因子：
--
作者：
Jackson SW;Scharping NE;Kolhatkar NS;Khim S;Schwartz MA;Li QZ;Hudkins KL;Alpers CE;Liggitt D;Rawlings DJ
通讯作者：
Rawlings DJ
DOI：
10.1084/jem.20151724
发表时间：
2016-05-02
期刊：
The Journal of experimental medicine
影响因子：
--
作者：
Jackson SW;Jacobs HM;Arkatkar T;Dam EM;Scharping NE;Kolhatkar NS;Hou B;Buckner JH;Rawlings DJ
通讯作者：
Rawlings DJ
DOI：
10.1084/jem.20130505
发表时间：
2014-01-13
期刊：
The Journal of experimental medicine
影响因子：
--
作者：
Goenka R;Matthews AH;Zhang B;O'Neill PJ;Scholz JL;Migone TS;Leonard WJ;Stohl W;Hershberg U;Cancro MP
通讯作者：
Cancro MP
影响因子：
--
作者：
Cardiel, Mario H.;Tumlin, James A.;Linnik, Matthew D.
通讯作者：
Linnik, Matthew D.
尖端：BAFF通过过渡B细胞的TACI依赖性激活促进自身抗体的产生。
DOI：
10.4049/jimmunol.1600017
发表时间：
2016-05-01
期刊：
Journal of immunology (Baltimore, Md. : 1950)
影响因子：
--
作者：
Jacobs HM;Thouvenel CD;Leach S;Arkatkar T;Metzler G;Scharping NE;Kolhatkar NS;Rawlings DJ;Jackson SW
通讯作者：
Jackson SW