| First Author | Pope MR | Year | 2015 |
| Journal | J Immunol | Volume | 194 |
| Issue | 3 | Pages | 1190-8 |
| PubMed ID | 25539820 | Mgi Jnum | J:331031 |
| Mgi Id | MGI:6870939 | Doi | 10.4049/jimmunol.1303124 |
| Citation | Pope MR, et al. (2015) TLR2 modulates antibodies required for intestinal ischemia/reperfusion-induced damage and inflammation. J Immunol 194(3):1190-8 |
| abstractText | 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, beta2-glycoprotein I (beta2-GPI). During reperfusion, binding of beta2-GPI by naturally occurring Abs results in an excessive inflammatory response that may lead to death. As beta2-GPI is critical for intestinal ischemia/reperfusion (IR)-induced tissue damage and TLR2 is one of the proposed receptors for beta2-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 beta2-GPI compared with wild-type mice, but beta2-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. |
