| First Author | Choi SM | Year | 2013 |
| Journal | J Exp Med | Volume | 210 |
| Issue | 3 | Pages | 551-61 |
| PubMed ID | 23401489 | Mgi Jnum | J:196462 |
| Mgi Id | MGI:5488544 | Doi | 10.1084/jem.20120260 |
| Citation | Choi SM, et al. (2013) Innate Stat3-mediated induction of the antimicrobial protein Reg3gamma is required for host defense against MRSA pneumonia. J Exp Med 210(3):551-61 |
| abstractText | Pulmonary Staphylococcus aureus (SA) infections are a public health concern and a major complication of hyper-IgE syndrome, caused by mutations in STAT3. In contrast to previous findings of skin infection, we observed that clearance of SA from the lung did not require T, B, or NK cells but did require Stat3 activation. Immunohistochemistry showed robust Stat3 phosphorylation in the lung epithelium. We identified that a critical Stat3 target gene in lung epithelium is Reg3g (regenerating islet-derived 3 gamma), a gene which is highly expressed in gastrointestinal epithelium but whose role in pulmonary host defense is uncharacterized. Stat3 regulated Reg3g transcription through direct binding at the Reg3g promoter region. Recombinant Reg3gamma bound to SA and had both bacteriostatic and bactericidal activity in a dose-dependent fashion. Stat3 inhibition in vivo reduced Reg3g transcripts in the lung, and more importantly, recombinant Reg3gamma rescued mice from defective SA clearance. These findings reveal an antibacterial function for lung epithelium through Stat3-mediated induction of Reg3gamma. |
