Αρχειοθήκη ιστολογίου

Αλέξανδρος Γ. Σφακιανάκης
ΩτοΡινοΛαρυγγολόγος
Αναπαύσεως 5
Άγιος Νικόλαος Κρήτη 72100
2841026182
6032607174

Τετάρτη 31 Ιανουαρίου 2018

ANKRD1 regulates innate immune responses against herpes simplex virus 1: A potential role in eczema herpeticum

Publication date: Available online 31 January 2018
Source:Journal of Allergy and Clinical Immunology
Author(s): Lianghua Bin, Xiaozhao Li, Brittany Richers, Joanne E. Streib, Jack W. Hu, Patricia Taylor, Donald Y.M. Leung
BackgroundAtopic dermatitis (AD) is a common inflammatory skin disease. A subset of AD is susceptible to disseminated herpes simplex virus (HSV) infection, a complication termed as eczema herpeticum(ADEH+). The immune mechanisms causing ADEH+ remain elusive. Using RNA-sequencing, we recently found that ankyrin repeat domain 1 (ANKRD1) was significantly induced in human peripheral blood mononuclear cells (PBMCs) upon HSV-1 stimulation; and its induction in ADEH+ was significantly reduced as compared to AD patients without a history of EH (ADEH-).ObjectiveTo validate ANKRD1 gene expression in non-atopic (NA), ADEH- and ADEH+ subjects; to delineate the biological function of ANKRD1 and the signaling pathway(s) involved.MethodsPurification of human PBMCs, monocytes, B cells, dendritic cells, T cells and NK cells; RNA extraction and qRT-PCR; small interfering RNA technique; co-immunoprecipitation; and western-blot assays were used.ResultsANKRD1 was significantly reduced in PBMCs from ADEH+ patients after HSV-1 stimulation as compared to PBMCs from ADEH-. We found that the induction of ANKRD1 by HSV-1 and multiple pathogen pattern recognition receptor (PRR) agonists are mediated by inflammatory cytokines. Silencing ANKRD1 gene expression in APCs led to increased viral load and reduced IFNb1 and IL-29 production. Using co-immunoprecipitation methods, we demonstrated that ANKRD1 formed protein complexes with IRF3 and IRF7, which are important transcription factors regulating PRRs' signaling transduction. Over-expression of ANKRD1 enhanced the IRF3-mediated signaling pathways.ConclusionANKRD1 is involved in IRF3 mediated anti-viral innate immune signaling pathways. Its reduced expression in ADEH+ subjects may contribute to the pathogenesis of ADEH+.



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