Science:过多的TLR7会引起自身免疫疾病-自主发布-资讯-生物在线

Science:过多的TLR7会引起自身免疫疾病

作者:上海研辉生物科技有限公司 2011-09-07T00:00 (访问量:4005)

BXSB小鼠是研究系统性红斑狼疮的主要模型,其Y染色体上的Yaa座位的复制能够加速自身免疫疾病倾向的小鼠发病。最新的研究表明,Yaa座位上TLR7基因的复制足以促进自身免疫疾病的发生。

来自美国的Bolland研究小组通过增加或者减少TLR7的基因量,研究了TLR7基因的复制在Yaa小鼠发病中的作用。首先,他们将Yaa小鼠与TLR7基因缺陷的小鼠进行杂交,使TLR7的基因量恢复到正常水平。在受TLR7的配体刺激时,这些小鼠脾脏细胞的增殖数量和野生型一致,RNA自身抗体的产生得到明显改善。然后将带有4个到32个TLR7基因拷贝的六种转基因小鼠与野生型小鼠进行比较,发现TLR7的表达强度与RNA自身抗体的产生和肾小球肾炎直接相关。并且,只要TLR7的表达量增加4至8倍,就会引起DC、T细胞和B细胞的明显活化。研究认为,TLR7及其相关的信号通路将可能成为治疗自身免疫疾病的潜在靶点。(科学网)

原始出处:

Immunity

Volume 27, Issue 5, 26 November 2007, Pages 801-810

doi:10.1016/j.immuni.2007.09.009

Control of Toll-like Receptor 7 Expression Is Essential to Restrict Autoimmunity and Dendritic Cell Proliferation

Jonathan A. Deane1, Prapaporn Pisitkun1, Rebecca S. Barrett1, Lionel Feigenbaum3, Terrence Town4, Jerrold M. Ward2, Richard A. Flavell4 and Silvia Bolland1, Corresponding Author Contact Information, E-mail The Corresponding Author
1Laboratory of Immunogenetics, NIAID/NIH, Rockville, MD 20852, USA
2Infectious Disease Pathogenesis Section, Comparative Medicine Branch, NIAID/NIH, Rockville, MD 20852, USA
3Laboratory Animal Science Program, Science Applications International Corporation (SAIC), NCI/NIH, Frederick, MD 21702, USA
4Section of Immunobiology, Yale University School of Medicine, New Haven, CT 06520, USA
Received 13 August 2007; revised 13 September 2007; accepted 17 September 2007. Published online: November 8, 2007. Available online 8 November 2007.

Summary

Nucleic acid-binding innate immune receptors such as Toll-like receptor 7 (TLR7)next term and TLR9 have been implicated in the development of some autoimmune pathologies. The Y chromosome-linked genomic modifier Yaa, which correlates with a duplication of previous termTlr7next term and 16 other genes, exacerbates lupus-like syndromes in several mouse strains. Here we demonstrated that duplication of the previous termTlr7next term gene was the sole requirement for this accelerated autoimmunity, because reduction of previous termTlr7next term gene dosage abolished the Yaa phenotype. Further, we described new transgenic lines that overexpressed previous termTLR7next term alone and found that spontaneous autoimmunity developed beyond a 2-fold increase in previous termTLR7next term expression. Whereas a modest increase in previous termTlr7next term gene dosage promoted autoreactive lymphocytes with RNA specificities and myeloid cell proliferation, a substantial increase in previous termTLR7next term expression caused fatal acute inflammatory pathology and profound dendritic cell dysregulation. These results underscore the importance of tightly regulating expression of previous termTLR7next term to prevent spontaneous triggering of harmful autoreactive and inflammatory responses.

Author Keywords: MOLIMMUNO; CELLIMMUNO

相关报道:

自身免疫性疾病

研究人员揭开金化合物能治疗自身免疫疾病的谜团

性别与自身免疫疾病

自身免疫疾病与干细胞治疗

绿茶具有预防自身免疫疾病的作用

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DNA疫苗可治疗自身免疫疾病

DNA疫苗可治疗自身免疫疾病

自身免疫性疾病的分类

自身免疫疾病与环境相关

通过调节性T细胞和效应性T细胞上的B7抗原结合预防自身免疫疾病

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