A new IRF-1–driven apoptotic pathway triggered by IL-4/IL-13 kills neonatal Th1 cells and weakens protection against viral infection

Mindy M. Miller, Subhasis Barik, Alexis N. Cattin-Roy, Tobechukwu K. Ukah, Christine Marie Hoeman, Habib Zaghouani*

*Corresponding author for this work

Research output: Contribution to journalArticle

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-4Ra/IL-13Ra1 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.

Original languageEnglish (US)
Pages (from-to)3173-3186
Number of pages14
JournalJournal of Immunology
Volume202
Issue number11
DOIs
StatePublished - Jun 1 2019

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Th1 Cells
Cytoprotection
Interleukin-13
Virus Diseases
Interleukin-4
Vaccination
Transcription Factors
Cytoplasm
Cell Death
Phosphorylation
Lymphocytes
Apoptosis
Cytokines
Genes
Proteins
Perinatal Death

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

Cite this

Miller, Mindy M. ; Barik, Subhasis ; Cattin-Roy, Alexis N. ; Ukah, Tobechukwu K. ; Hoeman, Christine Marie ; Zaghouani, Habib. / A new IRF-1–driven apoptotic pathway triggered by IL-4/IL-13 kills neonatal Th1 cells and weakens protection against viral infection. In: Journal of Immunology. 2019 ; Vol. 202, No. 11. pp. 3173-3186.
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A new IRF-1–driven apoptotic pathway triggered by IL-4/IL-13 kills neonatal Th1 cells and weakens protection against viral infection. / Miller, Mindy M.; Barik, Subhasis; Cattin-Roy, Alexis N.; Ukah, Tobechukwu K.; Hoeman, Christine Marie; Zaghouani, Habib.

In: Journal of Immunology, Vol. 202, No. 11, 01.06.2019, p. 3173-3186.

Research output: Contribution to journalArticle

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