Ankyrin repeat domain 1 regulates innate immune responses against herpes simplex virus 1: A potential role in eczema herpeticum.

Abstract

BACKGROUND:

Atopic dermatitis (AD) is a common inflammatory skin disease. A subset of patients with AD are susceptible to disseminated herpes simplex virus (HSV) infection, a complication termed 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 PBMCs upon HSV-1 stimulation, and its induction in patients with ADEH+ was significantly reduced compared with that seen in AD patients without a history of eczema herpeticum (ADEH-).

OBJECTIVE:

We sought to validate ANKRD1 gene expression in nonatopic (NA) subjects, patients with ADEH-, and patients with ADEH+ and to delineate the biological function of ANKRD1 and the signaling pathway or pathways involved.

METHODS:

Purification of human PBMCs, monocytes, B cells, dendritic cells, T cells, and natural killer cells; RNA extraction and quantitative RT-PCR; small interfering RNA technique; co-immunoprecipitation; and Western blot assays were used.

RESULTS:

ANKRD1 expression was significantly reduced in PBMCs from patients with ADEH+ after HSV-1 stimulation compared with PBMCs from patients with ADEH-. We found that the induction of ANKRD1 by HSV-1 and multiple pattern recognition receptor agonists are mediated by inflammatory cytokines. Silencing ANKRD1 gene expression in antigen-presenting cells led to increased viral load and reduced IFNB1 and IL29 production. Using co-immunoprecipitation methods, we demonstrated that ANKRD1 formed protein complexes with interferon regulatory factor (IRF) 3 and IRF7, which are important transcription factors regulating signaling transduction of pattern recognition receptors. Overexpression of ANKRD1 enhanced the IRF3-mediated signaling pathways.

CONCLUSION:

ANKRD1 is involved in IRF3-mediated antiviral innate immune signaling pathways. Its reduced expression in patients with ADEH+ might contribute to the pathogenesis of ADEH+.

• Authors: Lianghua Bin, Xiaozhao Li, Brittany Richers, Joanne E Streib, Jack W Hu, Patricia Taylor, Donald Y M Leung
• Journal: The Journal of allergy and clinical immunology (J Allergy Clin Immunol) Vol. 141 Issue 6 Pg. 2085-2093.e1 (06 2018) ISSN: 1097-6825 [Electronic] United States
• PMID: 29371118 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2018 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.

Chemical References

• ANKRD1 protein, human
• IRF3 protein, human
• Interferon Regulatory Factor-3
• Muscle Proteins
• Nuclear Proteins
• Repressor Proteins

Topics

• Adolescent
• Adult
• Aged
• Cells, Cultured
• Child
• Female
• Herpesvirus 1, Human (immunology)
• Humans
• Immunity, Innate (immunology)
• Interferon Regulatory Factor-3 (immunology)
• Kaposi Varicelliform Eruption (immunology)
• Leukocytes, Mononuclear
• Male
• Middle Aged
• Muscle Proteins (immunology)
• Nuclear Proteins (immunology)
• Repressor Proteins (immunology)
• Young Adult