| First Author | Orinska Z | Year | 2007 |
| Journal | Nat Med | Volume | 13 |
| Issue | 8 | Pages | 927-34 |
| PubMed ID | 17643110 | Mgi Jnum | J:125124 |
| Mgi Id | MGI:3723570 | Doi | 10.1038/nm1615 |
| Citation | Orinska Z, et al. (2007) IL-15 constrains mast cell-dependent antibacterial defenses by suppressing chymase activities. Nat Med 13(8):927-34 |
| abstractText | Sepsis remains a global clinical problem. By using the mouse cecal ligation and puncture model of sepsis, here we identify an important aspect of mast cell (MC)-dependent, innate immune defenses against Gram-negative bacteria by demonstrating that MC protease activity is regulated by interleukin-15 (IL-15). Mouse MCs express both constitutive and lipopolysaccharide-inducible IL-15 and store it intracellularly. Deletion of Il15 in mice markedly increases chymase activities, leading to greater MC bactericidal responses, increased processing and activation of neutrophil-recruiting chemokines, and significantly higher survival rates of mice after septic peritonitis. By showing that intracellular IL-15 acts as a specific negative transcriptional regulator of a mouse MC chymase (mast cell protease-2), we provide evidence that defined MC protease activity is transcriptionally regulated by an intracellularly retained cytokine. Our results identify an unexpected breach in MC-dependent innate immune defenses against sepsis and suggest that inhibiting intracellular IL-15 in MCs may improve survival from sepsis. |
