Cutting edge: AIM2 and endosomal TLRs differentially regulate arthritis and autoantibody production in DNase II-deficient mice.
Cutting edge: AIM2 and endosomal TLRs differentially regulate arthritis and autoantibody production in DNase II-deficient mice.
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DOI：
10.4049/jimmunol.1402573
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发表时间：
2015-02-01
期刊：
影响因子：
--
通讯作者：
Gravallese EM
中科院分区：
文献类型：
--
作者：
Baum R;Sharma S;Carpenter S;Li QZ;Busto P;Fitzgerald KA;Marshak-Rothstein A;Gravallese EM
先天免疫PRRs感知来自微生物的核酸并协调细胞因子的产生来解决感染。对宿主核酸的不恰当识别也会导致自身免疫性疾病。在这里，我们利用由自身DNA （DNase II−/−Ifnar−/−）累积引起的炎症模型来了解PRR感知途径在关节炎和自身抗体产生中的作用。利用DNase II/Ifnar缺失以及STING或AIM2 （TKO）缺失的小鼠，我们揭示了STING和AIM2通路在关节炎中的核心作用。AIM2 TKO小鼠表现出有限的炎性体激活，并且与STING TKO小鼠一样，关节炎症减轻。令人惊讶的是，AIM2和STING TKO小鼠维持自身抗体的产生，而DNase II - / - Ifnar - / -小鼠也缺乏TLR7/9内体定位所需的伴侣蛋白Unc93b，不能产生核酸自身抗体。总的来说，这些数据支持细胞质和内体核酸感应途径在疾病表现中的独特作用。
Innate immune PRRs sense nucleic acids from microbes and orchestrate cytokine production to resolve infection. Inappropriate recognition of host nucleic acids also results in autoimmune disease. Here we utilize a model of inflammation resulting from accrual of self DNA (DNase II−/− Ifnar−/−) to understand the role of PRR sensing pathways in arthritis and autoantibody production. Using mice deficient in DNase II/Ifnar together with deficiency in either STING or AIM2 (TKO), we reveal central roles for the STING and AIM2 pathway in arthritis. AIM2 TKO mice show limited inflammasome activation and, like STING TKO mice, have reduced inflammation in joints. Surprisingly, autoantibody production is maintained in AIM2 and STING TKO mice, while DNase II−/− Ifnar−/− mice also deficient in Unc93b, a chaperone required for TLR7/9 endosomal localization, fail to produce autoantibodies to nucleic acids. Collectively, these data support distinct roles for cytosolic and endosomal nucleic acid sensing pathways in disease manifestations.
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影响因子：
64.5
作者：
Stetson DB;Ko JS;Heidmann T;Medzhitov R
通讯作者：
Medzhitov R
DOI：
10.1056/nejmoa1312625
发表时间：
2014-08-07
期刊：
The New England journal of medicine
影响因子：
--
作者：
Liu Y;Jesus AA;Marrero B;Yang D;Ramsey SE;Sanchez GAM;Tenbrock K;Wittkowski H;Jones OY;Kuehn HS;Lee CR;DiMattia MA;Cowen EW;Gonzalez B;Palmer I;DiGiovanna JJ;Biancotto A;Kim H;Tsai WL;Trier AM;Huang Y;Stone DL;Hill S;Kim HJ;St Hilaire C;Gurprasad S;Plass N;Chapelle D;Horkayne-Szakaly I;Foell D;Barysenka A;Candotti F;Holland SM;Hughes JD;Mehmet H;Issekutz AC;Raffeld M;McElwee J;Fontana JR;Minniti CP;Moir S;Kastner DL;Gadina M;Steven AC;Wingfield PT;Brooks SR;Rosenzweig SD;Fleisher TA;Deng Z;Boehm M;Paller AS;Goldbach-Mansky R
通讯作者：
Goldbach-Mansky R
影响因子：
6.2
作者：
Walsh, Nicole C.;Reinwald, Susan;Gravallese, Ellen M.
通讯作者：
Gravallese, Ellen M.
影响因子：
12.3
作者：
Wu C;Orozco C;Boyer J;Leglise M;Goodale J;Batalov S;Hodge CL;Haase J;Janes J;Huss JW 3rd;Su AI
通讯作者：
Su AI
DOI：
10.1073/pnas.1215006109
发表时间：
2012-11-20
影响因子：
11.1
作者：
Ahn, Jeonghyun;Gutman, Delia;Barber, Glen N.
通讯作者：
Barber, Glen N.