TLR2 modulates antibodies required for intestinal ischemia/reperfusion-induced damage and inflammation.
TLR2 modulates antibodies required for intestinal ischemia/reperfusion-induced damage and inflammation.
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DOI：
10.4049/jimmunol.1303124
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发表时间：
2015-02-01
期刊：
影响因子：
--
通讯作者：
Fleming SD
中科院分区：
文献类型：
--
作者：
Pope MR;Fleming SD
在包括创伤和出血在内的多种临床条件下，再灌注放大了缺血性组织损伤。缺血诱导多种新抗原的表达，包括由血清蛋白β2-糖蛋白I（β2-GPI）2识别的脂质改变。在再灌注期间，β2-GPI与天然存在的抗体（Ab）的结合导致可能导致死亡的过度炎症反应。由于β2-GPI对肠缺血/再灌注（IR）诱导的组织损伤至关重要，Toll样受体2（TLR 2）是β2-GPI的拟议受体之一，我们假设IR诱导的肠损伤和炎症需要TLR 2。使用TLR 2 −/−小鼠，我们证明了TLR 2是IR诱导的粘膜损伤以及补体激活和促炎细胞因子产生所必需的。作为对IR的反应，与野生型小鼠相比，TLR 2 −/−小鼠的血清β2-GPI增加，但β2-GPI不沉积在缺血的肠组织上。此外，TLR 2-/-小鼠也不表达其他新抗原，这表明存在顺序反应。与其他TLR不同，TLR 2 −/−小鼠缺乏适当的抗体库来诱导肠道IR组织损伤或炎症。总之，这些数据表明，除了炎症反应，IR诱导的损伤需要TLR 2天然产生抗体。
In multiple clinical conditions including trauma and hemorrhage, reperfusion magnifies ischemic tissue damage. Ischemia induces expression of multiple neoantigens including lipid alterations which are recognized by the serum protein, β2-glycoprotein I (β2-GPI)2. During reperfusion, binding of β2-GPI by naturally occurring antibodies (Ab) results in an excessive inflammatory response which may lead to death. As β2-GPI is critical for intestinal ischemia/reperfusion (IR)-induced tissue damage and Toll-like receptor 2 (TLR2) is one of the proposed receptors for β2-GPI, we hypothesized that IR-induced intestinal damage and inflammation requires TLR2. Using TLR2−/− mice, we demonstrate that TLR2 is required for IR-induced mucosal damage, as well as complement activation and pro-inflammatory cytokine production. In response to IR, TLR2−/− mice have increased serum β2-GPI compared to wildtype mice but β2-GPI is not deposited on ischemic intestinal tissue. In addition, TLR2−/− mice also did not express other novel antigens suggesting a sequential response. Unlike other TLRs, TLR2−/− mice lacked the appropriate Ab repertoire to induce intestinal IR tissue damage or inflammation. Together, these data suggest that in addition to the inflammatory response, IR-induced injury requires TLR2 for naturally occurring Ab production.
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DOI：
10.4049/jimmunol.0803980
发表时间：
2009-05-01
期刊：
Journal of immunology (Baltimore, Md. : 1950)
影响因子：
--
作者：
Kulik L;Fleming SD;Moratz C;Reuter JW;Novikov A;Chen K;Andrews KA;Markaryan A;Quigg RJ;Silverman GJ;Tsokos GC;Holers VM
通讯作者：
Holers VM
影响因子：
7.5
作者：
Gao, Yin;Fang, Xiubin;Zhang, Baohui
通讯作者：
Zhang, Baohui
影响因子：
15.9
作者：
Leemans, JC;Stokman, G;Florquin, S
通讯作者：
Florquin, S
影响因子：
8.6
作者：
Fleming, SD;Mastellos, D;Tsokos, GC
通讯作者：
Tsokos, GC
DOI：
10.1161/atvbaha.107.140723
发表时间：
2007-05-01
影响因子：
8.7
作者：
Favre, Julie;Musette, Philippe;Richard, Vincent
通讯作者：
Richard, Vincent