Unknown,Transcriptomics,Genomics,Proteomics

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Contribution of the STAT1alpha and STAT1beta isoforms to IFN-gamma mediated innate immunity

ABSTRACT: The transcription factor STAT1 is essential for interferon- (IFN) mediated protective immunity in humans and mice. Two splice isoforms of STAT1, STAT1M-NM-1 and STAT1M-NM-2, differ with regard to a C-terminal transactivation domain, which is absent in STAT1M-NM-2. Dimers of STAT1M-NM-2 are therefore considered transcriptionally inactive and potential competitive inhibitors of STAT1M-NM-1. Contrasting this view, generation and analysis of mice deficient for either STAT1M-NM-1 or STAT1M-NM-2 demonstrated transcriptional activity of the STAT1M-NM-2 isoform and its enhancement of innate immunity. Gene expression profiling in primary cells revealed overlapping, but also non-redundant and gene-specific activities of STAT1M-NM-1 and STAT1M-NM-2 in response to IFNM-NM-3. Consistently, both isoforms mediated protective, IFNM-NM-3-dependent immunity against the bacterium Listeria monocytogenes, although with remarkably different efficiency. In contrast, STAT1M-NM-1 and STAT1M-NM-2 were largely redundant for transcriptional responses to IFNM-NM-1/M-NM-2 and for IFNM-NM-1/M-NM-2-dependent antiviral activity. Collectively, our data shed new light on how STAT1 isoforms contribute to antimicrobial immunity. We treated macrophages of Stat1 delta alpha and Stat1 delta beta isoforms as well as Stat1 KO and Stat1 Wt mice with IFN gamma and Listeria to reveal differences in gene expression between isoforms and the two control genotypes.

ORGANISM(S): Mus musculus

SUBMITTER: Claus Vogl

PROVIDER: E-GEOD-48970 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

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Contribution of the STAT1alpha and STAT1beta isoforms to IFN-gamma mediated innate immunity

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