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  • TLR2 modulates antibodies required for intestinal ischemia/reperfusion-induced damage and inflammation.

TLR2 modulates antibodies required for intestinal ischemia/reperfusion-induced damage and inflammation.

Journal of immunology (Baltimore, Md. : 1950) (2014-12-30)
Michael R Pope, Sherry D Fleming
ABSTRACT

In multiple clinical conditions, including trauma and hemorrhage, reperfusion magnifies ischemic tissue damage. Ischemia induces expression of multiple neoantigens, including lipid alterations that are recognized by the serum protein, β2-glycoprotein I (β2-GPI). During reperfusion, binding of β2-GPI by naturally occurring Abs results in an excessive inflammatory response that may lead to death. As β2-GPI is critical for intestinal ischemia/reperfusion (IR)-induced tissue damage and TLR2 is one of the proposed receptors for β2-GPI, we hypothesized that IR-induced intestinal damage and inflammation require TLR2. Using TLR2(-/-) mice, we demonstrate that TLR2 is required for IR-induced mucosal damage, as well as complement activation and proinflammatory cytokine production. In response to IR, TLR2(-/-) mice have increased serum β2-GPI compared with wild-type mice, but β2-GPI is not deposited on ischemic intestinal tissue. In addition, TLR2(-/-) mice also did not express other novel Ags, 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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