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Transcriptional profiling unveils type I and II interferon networks in blood and tissues across diseases.

Transcriptional profiling unveils type I and II interferon networks in blood and tissues across diseases.

Authors :
Singhania A
Graham CM
Gabryšová L
Moreira-Teixeira L
Stavropoulos E
Pitt JM
Chakravarty P
Warnatsch A
Branchett WJ
Conejero L
Lin JW
Davidson S
Wilson MS
Bancroft G
Langhorne J
Frickel E
Sesay AK
Priestnall SL
Herbert E
Ioannou M
Wang Q
Humphreys IR
Dodd J
Openshaw PJM
Mayer-Barber KD
Jankovic D
Sher A
Lloyd CM
Baldwin N
Chaussabel D
Papayannopoulos V
Wack A
Banchereau JF
Pascual VM
O'Garra A
Source :
Nature communications [Nat Commun] 2019 Jun 28; Vol. 10 (1), pp. 2887. Date of Electronic Publication: 2019 Jun 28.
Publication Year :
2019

Abstract

Understanding how immune challenges elicit different responses is critical for diagnosing and deciphering immune regulation. Using a modular strategy to interpret the complex transcriptional host response in mouse models of infection and inflammation, we show a breadth of immune responses in the lung. Lung immune signatures are dominated by either IFN-γ and IFN-inducible, IL-17-induced neutrophil- or allergy-associated gene expression. Type I IFN and IFN-γ-inducible, but not IL-17- or allergy-associated signatures, are preserved in the blood. While IL-17-associated genes identified in lung are detected in blood, the allergy signature is only detectable in blood CD4 <superscript>+</superscript> effector cells. Type I IFN-inducible genes are abrogated in the absence of IFN-γ signaling and decrease in the absence of IFNAR signaling, both independently contributing to the regulation of granulocyte responses and pathology during Toxoplasma gondii infection. Our framework provides an ideal tool for comparative analyses of transcriptional signatures contributing to protection or pathogenesis in disease.

Details

Language :
English
ISSN :
2041-1723
Volume :
10
Issue :
1
Database :
MEDLINE
Journal :
Nature communications
Publication Type :
Academic Journal
Accession number :
31253760
Full Text :
https://doi.org/10.1038/s41467-019-10601-6