| First Author | Yang X | Year | 2013 |
| Journal | J Immunol | Volume | 190 |
| Issue | 5 | Pages | 2068-79 |
| PubMed ID | 23365080 | Mgi Jnum | J:193459 |
| Mgi Id | MGI:5468583 | Doi | 10.4049/jimmunol.1202661 |
| Citation | Yang X, et al. (2013) T Cell Ig Mucin-3 Promotes Homeostasis of Sepsis by Negatively Regulating the TLR Response. J Immunol 190(5):2068-79 |
| abstractText | Sepsis is an excessive inflammatory condition with a high mortality rate and limited prediction and therapeutic options. In this study, for the first time, to our knowledge, we found that downregulation and/or blockade of T cell Ig and mucin domain protein 3 (Tim-3), a negative immune regulator, correlated with severity of sepsis, suggesting that Tim-3 plays important roles in maintaining the homeostasis of sepsis in both humans and a mouse model. Blockade and/or downregulation of Tim-3 led to increased macrophage activation, which contributed to the systemic inflammatory response in sepsis, whereas Tim-3 overexpression in macrophages significantly suppressed TLR-mediated proinflammatory cytokine production, indicating that Tim-3 is a negative regulator of TLR-mediated immune responses. Cross-talk between the Tim-3 and TLR4 pathways makes TLR4 an important contributor to Tim-3-mediated negative regulation of the innate immune response. Tim-3 signaling inhibited LPS-TLR4-mediated NF-kappaB activation by increasing PI3K-AKT phosphorylation and A20 activity. This negative regulatory role of Tim-3 reflects a new adaptive compensatory and protective mechanism in sepsis victims, a finding of potential importance for modulating innate responses in these patients. |
