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, 2019 06 01.
Article
in En
| MEDLINE
| ID: mdl-30996000
ABSTRACT
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-4Rα/IL-13Rα1 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.
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Virus Diseases
/
Viral Vaccines
/
Interleukin-4
/
Th1 Cells
/
Interleukin-13
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Interferon Regulatory Factor-1
Limits:
Animals
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Humans
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Newborn
Language:
En
Journal:
J Immunol
Year:
2019
Document type:
Article