Atopic dermatitis complicated by eczema herpeticum is associated with HLA B7 and reduced interferon-γ-producing CD8+ T cells

Mathias, Rasika A.; Weinberg, Adriana; Boguniewicz, Mark; Zaccaro, Daniel; Schneider, Lynda C.; Hata, Tissa; Hanifin, Jon M.; Beck, Lisa A.; Barnes, Kathleen C.; Leung, D. Y. M.

doi:10.1111/bjd.12382

Cited by 20 publications

(29 citation statements)

References 11 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…However, the molecular mechanism underpinning the susceptibility to herpes virus infection remains poorly understood. Aberrations observed in eczema herpeticum patients point to the importance of impaired anti-viral immune response 10 , diminished activation of CD8+ cytotoxic T cells 11 , and production of indoleamine 2,3-dioxygenase by antigen presenting cells residing in the skin 12 . We and others have shown, that LCs play a central role in the regulation of CD8 T cell-mediated cytotoxic immunity through their unique ability to efficiently cross-present antigens and induce effective CD8 T cell responses 2, 3, 13 .…”

Section: Introductionmentioning

confidence: 99%

Petri Net computational modelling of Langerhans cell Interferon Regulatory Factor Network predicts their role in T cell activation

Polak

Ung

Masapust

et al. 2017

Sci Rep

View full text Add to dashboard Cite

Langerhans cells (LCs) are able to orchestrate adaptive immune responses in the skin by interpreting the microenvironmental context in which they encounter foreign substances, but the regulatory basis for this has not been established. Utilising systems immunology approaches combining in silico modelling of a reconstructed gene regulatory network (GRN) with in vitro validation of the predictions, we sought to determine the mechanisms of regulation of immune responses in human primary LCs. The key role of Interferon regulatory factors (IRFs) as controllers of the human Langerhans cell response to epidermal cytokines was revealed by whole transcriptome analysis. Applying Boolean logic we assembled a Petri net-based model of the IRF-GRN which provides molecular pathway predictions for the induction of different transcriptional programmes in LCs. In silico simulations performed after model parameterisation with transcription factor expression values predicted that human LC activation of antigen-specific CD8 T cells would be differentially regulated by epidermal cytokine induction of specific IRF-controlled pathways. This was confirmed by in vitro measurement of IFN-γ production by activated T cells. As a proof of concept, this approach shows that stochastic modelling of a specific immune networks renders transcriptome data valuable for the prediction of functional outcomes of immune responses.

show abstract

Section: Introductionmentioning

confidence: 99%

Petri Net computational modelling of Langerhans cell Interferon Regulatory Factor Network predicts their role in T cell activation

Polak

Ung

Masapust

et al. 2017

Sci Rep

View full text Add to dashboard Cite

show abstract

“…89,90 Our data show that petrolatum boosts the T H 1/IFN-g responses in patients with AD, potentially ameliorating a defective antiviral mechanism in patients who are prone to recurrent viral skin infections. Additionally, petrolatum occlusion resulted in reduced cellularity and strong induction of AMPs in AD skin, although to a lesser extent than in non-AD skin.…”

Section: Discussionmentioning

confidence: 76%

Petrolatum: Barrier repair and antimicrobial responses underlying this “inert” moisturizer

Czarnowicki

Malajian

Khattri

et al. 2016

Journal of Allergy and Clinical Immunology

133

108

View full text Add to dashboard Cite

show abstract

“…Recent studies have shown that the subset of patients with atopic dermatitis who are prone to eczema herpeticum (ADEH+) have a distinct phenotype; they have more severe atopic skin disease, are more likely to have a food allergy and asthma, and are more prone to cutaneous skin infections 2 7. Research into cell-mediated immunity defects in the ADEH+ group of patients has found an association with the human leucocyte antigen B7 allele and that expression of interferon (IFN)-γ was lower in CD8+ T cells and monocytes when exposed to HSV 8. An in vitro study has found that regulators of type I and type III IFNs, which are important in fighting HSV infections, are downregulated 9…”

Section: Discussionmentioning

confidence: 99%

A corneal dendritic lesion with a skin eruption: eczema herpeticum, an important differential diagnosis

2015

View full text Add to dashboard Cite

Eczema herpeticum is a rare and potentially life-threatening viral infection. We present the case of a 54-year-old man who presented to the emergency eye clinic with a dendritic ulcer and a facial rash. An initial diagnosis of herpes zoster ophthalmicus was suspected. On follow-up, the rash had begun to rapidly disseminate and was no longer respecting dermatome boundaries. A diagnosis of eczema herpeticum was made and appropriate treatment started. This case highlights the importance of a comprehensive history and close inspection of skin lesions in patients with herpetic eye disease.

show abstract

Atopic dermatitis complicated by eczema herpeticum is associated with HLA B7 and reduced interferon-γ-producing CD8+ T cells

Abstract: These data suggest that defects in viral-induced IFN-γ from CD8+ T cells contribute to the ADEH+ phenotype.

Cited by 20 publications

References 11 publications

Petri Net computational modelling of Langerhans cell Interferon Regulatory Factor Network predicts their role in T cell activation

Petri Net computational modelling of Langerhans cell Interferon Regulatory Factor Network predicts their role in T cell activation

Petrolatum: Barrier repair and antimicrobial responses underlying this “inert” moisturizer

A corneal dendritic lesion with a skin eruption: eczema herpeticum, an important differential diagnosis

Contact Info

Product

Resources

About