| First Author | Croker BA | Year | 2011 |
| Journal | J Immunol | Volume | 186 |
| Issue | 2 | Pages | 1131-9 |
| PubMed ID | 21160041 | Mgi Jnum | J:168769 |
| Mgi Id | MGI:4938215 | Doi | 10.4049/jimmunol.1002702 |
| Citation | Croker BA, et al. (2011) Neutrophils require SHP1 to regulate IL-1beta production and prevent inflammatory skin disease. J Immunol 186(2):1131-9 |
| abstractText | The regulation of neutrophil recruitment, activation, and disposal is pivotal for circumscribed inflammation. SHP1(Y208N/Y208N) mutant mice develop severe cutaneous inflammatory disease that is IL-1R dependent. Genetic reduction in neutrophil numbers and neutrophilic responses to infection is sufficient to prevent the spontaneous initiation of this disease. Neutrophils from SHP1(Y208N/Y208N) mice display increased pro-IL-1beta production due to altered responses to MyD88-dependent and MyD88-independent signals. The IL-1R-dependent inflammatory disease in SHP1(Y208N/Y208N) mice develops independently of caspase 1 and proteinase 3 and neutrophil elastase. In response to Fas ligand, a caspase 1-independent inducer of IL-1beta production, neutrophils from SHP1(Y208N/Y208N) mice produce elevated levels of IL-1beta but display reduced caspase 3 and caspase 7 activation. In neutrophils deficient in SHP1, IL-1beta induces high levels of pro-IL-1beta suggesting the presence of a paracrine IL-1beta loop. These data indicate that the neutrophil- and IL-1-dependent disease in SHP1(Y208N/Y208N) mice is a consequence of loss of negative regulation of TLR and IL-1R signaling. |
