| First Author | Miller MM | Year | 2019 |
| Journal | J Immunol | Volume | 202 |
| Issue | 11 | Pages | 3173-3186 |
| PubMed ID | 30996000 | Mgi Jnum | J:276217 |
| Mgi Id | MGI:6306212 | Doi | 10.4049/jimmunol.1800943 |
| Citation | Miller MM, et al. (2019) A New IRF-1-Driven Apoptotic Pathway Triggered by IL-4/IL-13 Kills Neonatal Th1 Cells and Weakens Protection against Viral Infection. J Immunol 202(11):3173-3186 |
| abstractText | Early life immune responses are deficient in Th1 lymphocytes that compromise neonatal vaccination. We found that IL-4 and IL-13 engage a developmentally expressed IL-4Ralpha/IL-13Ralpha1 heteroreceptor to endow IFN regulatory factor 1 (IRF-1) with apoptotic functions, which redirect murine neonatal Th1 reactivation to cell death. IL-4/IL-13-induced STAT6 phosphorylation serves to enhance IRF-1 transcription and promotes its egress from the nucleus. In the cytoplasm, IRF-1 can no longer serve as an anti-viral transcription factor but, instead, colocalizes with Bim and instigates the mitochondrial, or intrinsic, death pathway. The new pivotal function of IRF-1 in the death of neonatal Th1 cells stems from the ability of its gene to bind STAT6 for enhanced transcription and the proficiency of its protein to precipitate Bim-driven apoptosis. This cytokine-induced, IRF-1-mediated developmental death network weakens neonatal Th1 responses during early life vaccination and increases susceptibility to viral infection. |
