| First Author | Heinonen KM | Year | 2004 |
| Journal | Blood | Volume | 103 |
| Issue | 9 | Pages | 3457-64 |
| PubMed ID | 14726372 | Mgi Jnum | J:90541 |
| Mgi Id | MGI:3044093 | Doi | 10.1182/blood-2003-09-3153 |
| Citation | Heinonen KM, et al. (2004) T-cell protein tyrosine phosphatase deletion results in progressive systemic inflammatory disease. Blood 103(9):3457-64 |
| abstractText | The deregulation of the immune response is a critical component in inflammatory disease. Recent in vitro data show that T-cell protein tyrosine phosphatase (TC-PTP) is a negative regulator of cytokine signaling. Furthermore, tc-ptp(-/-) mice display immune defects and die within 5 weeks of birth. We report here that tc-ptp(-/-) mice develop progressive systemic inflammatory disease as shown by chronic myocarditis, gastritis, nephritis, and sialadenitis as well as elevated serum interferon-gamma. The widespread mononuclear cellular infiltrates correlate with exaggerated interferon-gamma, tumor necrosis factor-alpha, interleukin-12, and nitric oxide production in vivo. Macrophages grown from tc-ptp(-/-) mice are inherently hypersensitive to lipopolysaccharide, which can also be detected in vivo as an increased susceptibility to endotoxic shock. These results identify T-cell protein tyrosine phosphatase as a key modulator of inflammatory signals and macrophage function. |
