Type i IFN is necessary and sufficient for inflammation-induced red blood cell alloimmunization in mice

David R. Gibb, Jingchun Liu, Prabitha Natarajan, Manjula Santhanakrishnan, David J. Madrid, Stephanie C. Eisenbarth, James C. Zimring, Akiko Iwasaki, Jeanne E. Hendrickson*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

31 Scopus citations

Abstract

During RBC transfusion, production of alloantibodies against RBC non-ABO Ags can cause hemolytic transfusion reactions and limit availability of compatible blood products, resulting in anemia-associated morbidity and mortality. Multiple studies have established that certain inflammatory disorders and inflammatory stimuli promote alloimmune responses to RBC Ags. However, the molecular mechanisms underlying these findings are poorly understood. Type I IFNs (IFN-α/β) are induced in inflammatory conditions associated with increased alloimmunization. By developing a new transgenic murine model, we demonstrate that signaling through the IFN-α/β receptor is required for inflammation-induced alloimmunization. Additionally, mitochondrial antiviral signaling protein-mediated signaling through cytosolic pattern recognition receptors was required for polyinosinicpolycytidylic acid-induced IFN-α/β production and alloimmunization. We further report that IFN-α, in the absence of an adjuvant, is sufficient to induce RBC alloimmunization. These findings raise the possibility that patients with IFN-α/β-mediated conditions, including autoimmunity and viral infections, may have an increased risk of RBC alloimmunization and may benefit from personalized transfusion protocols and/or targeted therapies.

Original languageEnglish (US)
Pages (from-to)1041-1050
Number of pages10
JournalJournal of Immunology
Volume199
Issue number3
DOIs
StatePublished - Aug 1 2017
Externally publishedYes

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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