Cytokines pre-determined by genetic factors are involved in pathogenesis of Rheumatoid arthritis.
Cytokines pre-determined by genetic factors are involved in pathogenesis of Rheumatoid arthritis.
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DOI：
10.1016/j.cyto.2014.11.028
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发表时间：
2015-10
期刊：
影响因子：
3.8
通讯作者：
Taneja, Veena
中科院分区：
文献类型：
--
作者：
Taneja, Veena
类风湿性关节炎（RA）与产生促炎细胞因子的自身反应性CD 4 T细胞的存在有关。遗传因素在RA易感性中的作用得到了患者中某些HLA II类分子存在增加的有力支持。HLA II类基因是高度多态性的，并且对于产生对清除感染的免疫应答至关重要。由CD 4 T细胞产生的Th 1和Th 17应答有助于清除感染。HLA-DQ 8是一种混杂的结合剂，并呈递许多产生免疫应答和产生Th 17应答的肽。DRB 1 *0401与IL-17和IFN-γ的产生相关。因此，DR 4和DQ 8都可以通过产生TH 1/Th 17细胞因子来清除感染，但它们的存在会增加患RA的风险。使用转基因小鼠表达人类HLA基因，我们已经表明，HLA多态性决定细胞因子谱。DRB 1 *04分子调节DQ 8限制性反应，并决定携带DR 4/DQ 8单倍型小鼠关节炎的结果。因此，DQ和DR分子之间的相互作用决定了细胞因子环境和HLA单倍型倾向于自身免疫。
Rheumatoid arthritis (RA) is associated with the presence of autoreactive CD4 T cells that produce pro-inflammatory cytokines. The role of genetic factors in the predilection to develop RA is strongly supported by the increased presence of certain HLA class II molecules in patients. The HLA class II genes are highly polymorphic and are critical for generating an immune response to clear infections. Production of Th1 and Th17 response by the CD4 T cells helps to clear infections. HLA-DQ8 is a promiscuous binder and presents many peptides generating immune response and producing a Th17 response. DRB1*0401 is associated with the production of both IL-17 and IFN-γ. Thus both DR4 and DQ8 can clear infections by producing TH1/Th17 cytokines, but their presence increases the risk of developing RA. Using transgenic mice expressing human HLA genes, we have shown that HLA polymorphism determines the cytokine profile. DRB1*04 molecules modulate the DQ8-restricted response and determine the outcome of arthritis in mice carrying DR4/DQ8 haplotype. Thus, interaction between DQ and DR molecules determines the cytokine milieu and propensity of the HLA haplotype to predispose to autoimmunity.
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影响因子：
--
作者：
Davis, John M., III;Knutson, Keith L.;Gabriel, Sherine E.
通讯作者：
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影响因子：
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作者：
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通讯作者：
Criswell, Lindsey A.
DOI：
10.1111/j.1600-0897.2004.00177.x
发表时间：
2004-07-01
影响因子：
3.6
作者：
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通讯作者：
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影响因子：
12.8
作者：
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通讯作者：
Taneja, Veena
影响因子：
13.6
作者：
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通讯作者：
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