Structural basis of a unique interferon-beta signaling axis mediated via the receptor IFNAR1

Nicole Anne De Weerd; Julian Vivian; Thao K Nguyen; Niamh Mangan; Jodee Ann Gould; Susie-Jane Braniff; Leyla Zaker-Tabrizi; Ka Yee Fung; Samuel Forster; Travis Clarke Beddoe; Hugh Harrington Reid; Jamie Rossjohn; Paul John Hertzog

doi:10.1038/ni.2667

Structural basis of a unique interferon-beta signaling axis mediated via the receptor IFNAR1

Nicole Anne De Weerd, Julian Vivian, Thao K Nguyen, Niamh Mangan, Jodee Ann Gould, Susie-Jane Braniff, Leyla Zaker-Tabrizi, Ka Yee Fung, Samuel Forster, Travis Clarke Beddoe, Hugh Harrington Reid, Jamie Rossjohn, Paul John Hertzog

Research output: Contribution to journal › Article › Research › peer-review

205 Citations (Scopus)

Abstract

Type I interferons are important in regulating immune responses to pathogens and tumors. All interferons are considered to signal via the heterodimeric IFNAR1-IFNAR2 complex, yet some subtypes such as interferon-beta (IFN-beta) can exhibit distinct functional properties, although the molecular basis of this is unclear. Here we demonstrate IFN-beta can uniquely and specifically ligate to IFNAR1 in an IFNAR2-independent manner, and we provide the structural basis of the IFNAR1-IFN-beta interaction. The IFNAR1-IFN-beta complex transduced signals that modulated expression of a distinct set of genes independently of Jak-STAT pathways. Lipopolysaccharide-induced sepsis was ameliorated in Ifnar1(-/-) mice but not Ifnar2(-/-) mice, suggesting that IFNAR1-IFN-beta signaling is pathologically relevant. Thus, we provide a molecular basis for understanding specific functions of IFN-beta.

Original language	English
Pages (from-to)	901 - 907
Number of pages	7
Journal	Nature Immunology
Volume	14
Issue number	9
DOIs	https://doi.org/10.1038/ni.2667
Publication status	Published - 2013

Access to Document

10.1038/ni.2667

Cite this

@article{1aebecf3adf14606884fd99e87046b9c,

title = "Structural basis of a unique interferon-beta signaling axis mediated via the receptor IFNAR1",

abstract = "Type I interferons are important in regulating immune responses to pathogens and tumors. All interferons are considered to signal via the heterodimeric IFNAR1-IFNAR2 complex, yet some subtypes such as interferon-beta (IFN-beta) can exhibit distinct functional properties, although the molecular basis of this is unclear. Here we demonstrate IFN-beta can uniquely and specifically ligate to IFNAR1 in an IFNAR2-independent manner, and we provide the structural basis of the IFNAR1-IFN-beta interaction. The IFNAR1-IFN-beta complex transduced signals that modulated expression of a distinct set of genes independently of Jak-STAT pathways. Lipopolysaccharide-induced sepsis was ameliorated in Ifnar1(-/-) mice but not Ifnar2(-/-) mice, suggesting that IFNAR1-IFN-beta signaling is pathologically relevant. Thus, we provide a molecular basis for understanding specific functions of IFN-beta.",

author = "{De Weerd}, {Nicole Anne} and Julian Vivian and Nguyen, {Thao K} and Niamh Mangan and Gould, {Jodee Ann} and Susie-Jane Braniff and Leyla Zaker-Tabrizi and Fung, {Ka Yee} and Samuel Forster and Beddoe, {Travis Clarke} and Reid, {Hugh Harrington} and Jamie Rossjohn and Hertzog, {Paul John}",

year = "2013",

doi = "10.1038/ni.2667",

language = "English",

volume = "14",

pages = "901 -- 907",

journal = "Nature Immunology",

issn = "1529-2908",

publisher = "Nature Publishing Group",

number = "9",

}

TY - JOUR

T1 - Structural basis of a unique interferon-beta signaling axis mediated via the receptor IFNAR1

AU - De Weerd, Nicole Anne

AU - Vivian, Julian

AU - Nguyen, Thao K

AU - Mangan, Niamh

AU - Gould, Jodee Ann

AU - Braniff, Susie-Jane

AU - Zaker-Tabrizi, Leyla

AU - Fung, Ka Yee

AU - Forster, Samuel

AU - Beddoe, Travis Clarke

AU - Reid, Hugh Harrington

AU - Rossjohn, Jamie

AU - Hertzog, Paul John

PY - 2013

Y1 - 2013

N2 - Type I interferons are important in regulating immune responses to pathogens and tumors. All interferons are considered to signal via the heterodimeric IFNAR1-IFNAR2 complex, yet some subtypes such as interferon-beta (IFN-beta) can exhibit distinct functional properties, although the molecular basis of this is unclear. Here we demonstrate IFN-beta can uniquely and specifically ligate to IFNAR1 in an IFNAR2-independent manner, and we provide the structural basis of the IFNAR1-IFN-beta interaction. The IFNAR1-IFN-beta complex transduced signals that modulated expression of a distinct set of genes independently of Jak-STAT pathways. Lipopolysaccharide-induced sepsis was ameliorated in Ifnar1(-/-) mice but not Ifnar2(-/-) mice, suggesting that IFNAR1-IFN-beta signaling is pathologically relevant. Thus, we provide a molecular basis for understanding specific functions of IFN-beta.

AB - Type I interferons are important in regulating immune responses to pathogens and tumors. All interferons are considered to signal via the heterodimeric IFNAR1-IFNAR2 complex, yet some subtypes such as interferon-beta (IFN-beta) can exhibit distinct functional properties, although the molecular basis of this is unclear. Here we demonstrate IFN-beta can uniquely and specifically ligate to IFNAR1 in an IFNAR2-independent manner, and we provide the structural basis of the IFNAR1-IFN-beta interaction. The IFNAR1-IFN-beta complex transduced signals that modulated expression of a distinct set of genes independently of Jak-STAT pathways. Lipopolysaccharide-induced sepsis was ameliorated in Ifnar1(-/-) mice but not Ifnar2(-/-) mice, suggesting that IFNAR1-IFN-beta signaling is pathologically relevant. Thus, we provide a molecular basis for understanding specific functions of IFN-beta.

UR - http://www.nature.com/ni/journal/v14/n9/pdf/ni.2667.pdf

U2 - 10.1038/ni.2667

DO - 10.1038/ni.2667

M3 - Article

SN - 1529-2908

VL - 14

SP - 901

EP - 907

JO - Nature Immunology

JF - Nature Immunology

IS - 9

ER -

Structural basis of a unique interferon-beta signaling axis mediated via the receptor IFNAR1

Abstract

Access to Document

Other files and links

The role of a novel protein, interferon epsilon, in reproductive tract immunity

The role of a novel cytokine of the innate immune response in viral infection

Cite this

Structural basis of a unique interferon-beta signaling axis mediated via the receptor IFNAR1

Abstract

Access to Document

Other files and links

Projects

The role of a novel protein, interferon epsilon, in reproductive tract immunity

The role of a novel cytokine of the innate immune response in viral infection

Cite this