Negative regulation of IFN-α/β signaling by IFN regulatory factor 2 for homeostatic development of dendritic cells

Kenya Honda, Tatsuaki Mizutani, Tadatsugu Taniguchi

Research output: Contribution to journalArticle

80 Citations (Scopus)

Abstract

The development and cooperation of distinct subsets of antigen-presenting cells, particularly dendritic cells (DCs), may be critical for maintaining homeostatic immune responses. Recently, much attention has been focused on IFN-α/β, the cytokines induced en masse by virus infection or the activation of Toll-like receptors, in the context of DC activation. Here, we show that mice deficient in IFN regulatory factor 2 exhibit selective loss of CD8α- DCs, the so-called myeloid DCs, which is accompanied by a notable increase in CD11c-CD11bhigh other myeloid lineage cells. Such deficiency is intrinsic to the bone marrow precursors, in which the abnormal induction of IFN-α/β genes causes excessive IFN signaling. The critical function of IFN regulatory factor 2 in the negative regulation of IFN-α/β signaling is underscored by the observation that the deficiency is rescued by introducing an additional null mutation for the IFN receptor complex. In view of accumulating evidence of the critical role of IFN-α/β signaling in DC activation, our present study offers a unique example in that the magnitude of a cytokine signal should be properly balanced in a stage-specific manner during the differentiation and activation of DCs.

Original languageEnglish
Pages (from-to)2416-2421
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume101
Issue number8
DOIs
Publication statusPublished - 2004 Feb 22
Externally publishedYes

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Dendritic Cells
Myeloid Cells
Cytokines
Toll-Like Receptors
Antigen-Presenting Cells
Virus Diseases
Bone Marrow
Mutation
Genes

ASJC Scopus subject areas

  • Genetics
  • General

Cite this

Negative regulation of IFN-α/β signaling by IFN regulatory factor 2 for homeostatic development of dendritic cells. / Honda, Kenya; Mizutani, Tatsuaki; Taniguchi, Tadatsugu.

In: Proceedings of the National Academy of Sciences of the United States of America, Vol. 101, No. 8, 22.02.2004, p. 2416-2421.

Research output: Contribution to journalArticle

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