Cutting edge: protein phosphatase 2A confers susceptibility to autoimmune disease through an IL-17-dependent mechanism.
Cutting edge: protein phosphatase 2A confers susceptibility to autoimmune disease through an IL-17-dependent mechanism.
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DOI：
10.4049/jimmunol.1200143
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发表时间：
2012-04-15
期刊：
影响因子：
--
通讯作者：
Tsokos GC
中科院分区：
文献类型：
--
作者：
Crispín JC;Apostolidis SA;Rosetti F;Keszei M;Wang N;Terhorst C;Mayadas TN;Tsokos GC
系统性红斑狼疮（SLE）是一种累及多个器官的自身免疫性疾病，由于存在大量的混杂因素，个体分子畸变在SLE发病机制中的作用往往难以评估。为了评估T细胞中磷酸酶PP 2A表达增加的影响，如在SLE患者中所记录的，我们产生了在T细胞中过表达PP 2Ac亚基的转基因小鼠。转基因小鼠在没有其他免疫缺陷的情况下显示出对免疫介导的肾小球肾炎的高度易感性。CD 4 + T细胞产生增加量的IL-17，而外周血中的嗜中性粒细胞的数量增加。IL-17中和作用可消除肾小球肾炎的发展。我们的结论是PP 2Ac表达增加参与SLE的发病机制，通过促进炎症通过未经检查的IL-17的生产和促进终末器官损伤的发展。
The contribution of individual molecular aberrations to the pathogenesis of systemic lupus erythematosus (SLE), an autoimmune disease that affects multiple organs, is often difficult to evaluate because of the presence of abundant confounding factors. To assess the effect of increased expression of the phosphatase PP2A in T cells, as recorded in SLE patients, we generated a transgenic mouse that overexpresses the PP2Ac subunit in T cells. The transgenic mouse displays a heightened susceptibility to immune-mediated glomerulonephritis in the absence of other immune defects. CD4+ T cells produce increased amounts of IL-17 while the number of neutrophils in the peripheral blood is increased. IL-17 neutralization abrogated the development of glomerulonephritis. We conclude that increased PP2Ac expression participates in SLE pathogenesis by promoting inflammation through unchecked IL-17 production and facilitating the development of end-organ damage.
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影响因子：
13.6
作者：
Mayadas TN;Rosetti F;Ernandez T;Sethi S
通讯作者：
Sethi S
对全身性红斑狼疮的遗传基础的最新见解。
影响因子：
5
作者：
Moser, K. L.;Kelly, J. A.;Lessard, C. J.;Harley, J. B.
通讯作者：
Harley, J. B.
影响因子：
30.5
作者：
Doreau, Agnes;Belot, Alexandre;Bonnefoy-Berard, Nathalie
通讯作者：
Bonnefoy-Berard, Nathalie
影响因子：
4.4
作者：
Thomas, Rajan M.;Chunder, Neelanjana;Wells, Andrew D.
通讯作者：
Wells, Andrew D.
影响因子：
--
作者：
Tan, Wenfeng;Sunahori, Katsue;Zhao, Jian;Deng, Yun;Kaufman, Kenneth M.;Kelly, Jennifer A.;Langefeld, Carl D.;Williams, Adrienne H.;Comeau, Mary E.;Ziegler, Julie T.;Marion, Miranda C.;Bae, Sang-Cheol;Lee, Joo Hyun;Lee, Ji-Seon;Chang, Deh-Ming;Song, Yeong Wook;Yu, Chack-Yung;Kimberly, Robert P.;Edberg, Jeffrey C.;Brown, Elizabeth E.;Petri, Michelle A.;Ramsey-Goldman, Rosalind;Vila, Luis M.;Reveille, John D.;Alarcon-Riquelme, Marta E.;Harley, John B.;Boackle, Susan A.;Stevens, Anne M.;Scofield, R. Hal;Merrill, Joan T.;Freedman, Barry I.;Anaya, Juan-Manuel;Criswell, Lindsey A.;Jacob, Chaim O.;Vyse, Timothy J.;Niewold, Timothy B.;Gaffney, Patrick M.;Moser, Kathy L.;Gilkeson, Gary S.;Kamen, Diane L.;James, Judith A.;Grossman, Jennifer M.;Hahn, Bevra H.;Tsokos, George C.;Tsao, Betty P.
通讯作者：
Tsao, Betty P.