Cigarette Smoke Induces Immune Responses to Vimentin in both, Arthritis-Susceptible and -Resistant Humanized Mice.
Cigarette Smoke Induces Immune Responses to Vimentin in both, Arthritis-Susceptible and -Resistant Humanized Mice.
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DOI：
10.1371/journal.pone.0162341
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发表时间：
2016
期刊：
影响因子：
3.7
通讯作者：
Taneja V
中科院分区：
文献类型：
--
作者：
Bidkar M;Vassallo R;Luckey D;Smart M;Mouapi K;Taneja V
类风湿性关节炎（RA）是一种以慢性滑膜炎症为特征的自身免疫性疾病，其发病机制与遗传和环境因素有关。人类白细胞抗原（HLA）DRB 1 *0401与RA的易感性相关，而香烟烟雾（CS）暴露促进血清阳性疾病，DRB 1 *0401+个体的严重程度增加。吸烟者有较高水平的瓜氨酸肽抗体。在这项研究中，我们确定是否响应一个已知的自身抗原，波形蛋白（Vim）是共享表位特异性和CS如何影响这种反应使用转基因小鼠携带RA敏感，*0401，和抗，*0402，基因。在相对短暂的暴露于CS后，鼠肺中肽基精氨酸脱亚胺酶（PAD）的表达增加。吸烟导致 *0401小鼠脾细胞产生干扰素（IFN）-γ，同时降低白细胞介素（IL）-10水平。相比之下，CS增加Th 2细胞因子沿着T调节细胞在 *0402小鼠。CS暴露后，在两种品系的未处理小鼠中观察到天然和瓜氨酸化Vim抗体水平增加。我们的数据表明，关节炎易感和耐药小鼠可以产生细胞和体液免疫Vim，但CS诱导的调节宿主免疫是依赖于与宿主HLA基因的相互作用。
Rheumatoid arthritis (RA) is an autoimmune disease marked by chronic synovial inflammation and both, genetic and environmental factors are involved in its pathogenesis. Human leukocyte antigen (HLA) DRB1*0401 is associated with susceptibility to develop RA, while cigarette smoke (CS) exposure promotes seropositive disease with increased severity in DRB1*0401+ individuals. Smokers have higher levels of antibodies against citrullinated peptides. In this study, we determined whether the response to a known autoantigen, Vimentin (Vim) is shared epitope specific and how CS influences this response using transgenic-mice carrying RA-susceptible,*0401, and -resistant, *0402, genes. Following relatively brief exposure to CS, peptidyl arginine deiminase (PAD) enzyme expression was increased in murine lungs. Cigarette smoking led to production of Interferon (IFN)-γ with reduced levels of Interleukin (IL)-10 by splenocytes of *0401 mice. In contrast, CS augmented Th2 cytokines along with T-regulatory cells in *0402 mice. An increase in levels of antibodies to native and citrullinated Vim was observed in naïve mice of both strains following CS exposure. Our data showed that both arthritis-susceptible and -resistant mice can generate cellular and humoral immunity to Vim; however CS-induced modulation of host immunity is dependent on the interaction with the host HLA genes.
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影响因子：
--
作者：
Lundstrom, Erneli;Kallberg, Henrik;Alfredsson, Lars;Klareskog, Lars;Padyukov, Leonid
通讯作者：
Padyukov, Leonid
影响因子：
--
作者：
Snir, Omri;Rieck, Mary;Gebe, John A.;Yue, Betty B.;Rawlings, Crystal A.;Nepom, Gerald;Malmstrom, Vivianne;Buckner, Jane H.
通讯作者：
Buckner, Jane H.
影响因子：
15.9
作者：
Ma, B;Kang, MJ;Elias, JA
通讯作者：
Elias, JA
影响因子：
12.8
作者：
Behrens, Marshall;Trejo, Theodore;Taneja, Veena
通讯作者：
Taneja, Veena
DOI：
10.1186/ar86
发表时间：
2000
期刊：
Arthritis research
影响因子：
--
作者：
Kinne RW;Bräuer R;Stuhlmüller B;Palombo-Kinne E;Burmester GR
通讯作者：
Burmester GR