Natural Interferon α/β–Producing Cells Link Innate and Adaptive Immunity

By N. Kadowaki, S. Antonenko, J. Lau, Yong‐jun Liu. Journal of Experimental Medicine, 2000

889 citations recorded by the source corpus.

Innate immune responses to pathogens critically impact the development of adaptive immune responses. However, it is not completely understood how innate immunity controls the initiation of adaptive immunities or how it determines which type of adaptive immunity will be induced to eliminate a given pathogen. Here we show that viral stimulation not only triggers natural interferon (IFN)-α/β–producing cells (IPCs) to produce vast amounts of antiviral IFN-α/β but also induces these cells to differentiate into dendritic cells (DCs). IFN-α/β and tumor necrosis factor α produced by virus-activated IPCs act as autocrine survival and DC differentiation factors, respectively. The virus-induced DCs stimulate naive CD4+ T cells to produce IFN-γ and interleukin (IL)-10, in contrast to IL-3–induced DCs, which stimulate naive CD4+ T cells to produce T helper type 2 cytokines IL-4, IL-5, and IL-10. Thus, IPCs may play two master roles in antiviral immune responses: directly inhibiting viral replication by producing large amounts of IFN-α/β, and subsequently triggering adaptive T cell–mediated immunity by differentiating into DCs. IPCs constitute a critical link between innate and adaptive immunity.

Subfields: Immunology

View Paper: https://www.semanticscholar.org/paper/dd4ef0c6c05ce85574b25c2d96d9f23969bd3bc3

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In Immunology

1. Jacques Banchereau
2. Yong‐jun Liu
3. W. Zou
4. V. Pascual
5. A. Lanzavecchia
6. F. Sallusto
7. A. Palucka
8. M. Gilliet

Citations in the corpus

• Plasmacytoid dendritic cells prime IL-10–producing T regulatory cells by inducible costimulator ligand (2007, background): “This cytokine profi le is consistent with a Th1like response as previously reported (25).”
• Microbial Compounds Selectively Induce Th1 Cell-Promoting or Th2 Cell-Promoting Dendritic Cells In Vitro with Diverse Th Cell-Polarizing Signals1 (2002, background): “Liu and coworkers (26) showed that plasmacytoid DCs activated with influenza virus promote the development of Th1 cells via IFN- .”
• Regulation of T cell immunity by dendritic cells. (2001, background): “Thus, the Th1-polarizing capacity of DCs is contingent on a number of variables pathic effects of viruses (Cella et al., 2000; Kadowaki et al., 2000).that include the microenvironment, the maturation stim- Recruitment of DC precursors (monocytes) into peripheral tissues and maturation of DCs in…”
• Plasmacytoid predendritic cells initiate psoriasis through interferon-α production (2005, background): “Upon viral stimulation, PDCs differentiate into DCs (11, 12) and/ or induce an IFN- –dependent maturation of bystander myeloid DCs with the ability to drive Th1 responses (13), thus providing a unique link between innate and adaptive antiviral immunity.”
• Plasmacytoid dendritic cells induce plasma cell differentiation through type I interferon and interleukin 6. (2003, background): “Here pDCs differentiate into mature DCs able to induce the we report that depletion of pDCs from human blood differentiation of CD4 T cells into IFN- - and IL-10mononuclear cells abrogates the secretion of specific secreting cells (Kadowaki et al., 2000).”