Cutaneous Immune Cell-Microbiota Interactions Are Controlled by Epidermal JunB/AP-1

Cutaneous Immune Cell-Microbiota Interactions Are Controlled by Epidermal JunB/AP-1.

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Item Type: Article
Status: Published
Official URL: https://doi.org/10.1016/j.celrep.2019.09.042
Journal or Publication Title: Cell Reports
Volume: 29
Number: 4
Page Range: 844-859.e3
Date: 2019
Divisions: Immune Imaging
Depositing User: General Admin
Identification Number: 10.1016/j.celrep.2019.09.042
ISSN: 22111247
Date Deposited: 21 Dec 2020 23:25
Abstract:

Atopic dermatitis (AD) is a multi-factorial skin disease with a complex inflammatory signature including type 2 and type 17 activation. Although colonization by S. aureus is common in AD, the mechanisms rendering an organism prone to dysbiosis, and the role of IL-17A in the control of S. aureus-induced skin inflammation, are not well understood. Here, we show several pathological aspects of AD, including type 2/type 17 immune responses, elevated IgE, barrier dysfunction, pruritus, and importantly, spontaneous S. aureus colonization in JunBΔep mice, with a large transcriptomic overlap with AD. Additionally, using Rag1-/- mice, we demonstrate that adaptive immune cells are necessary for protection against S. aureus colonization. Prophylactic antibiotics, but not antibiotics after established dysbiosis, reduce IL-17A expression and skin inflammation, examined using Il17a-eGFP reporter mice. Mechanistically, keratinocytes lacking JunB exhibit higher MyD88 levels in vitro and in vivo, previously shown to regulate S. aureus colonization. In conclusion, our data identify JunB as an upstream regulator of microbiota-immune cell interactions and characterize the IL-17A response upon spontaneous dysbiosis.

Keywords: AP-1; JunB; atopic dermatitis; dysbiosis; microbiota; skin inflammation; type 2 immunity.

Copyright © 2019 The Authors. Published by Elsevier Inc. All rights reserved.

Creators:
Creators
Email
Uluçkan, Özge
UNSPECIFIED
Jiménez, Maria
UNSPECIFIED
Roediger, Ben
UNSPECIFIED
Schnabl, Jakob
UNSPECIFIED
Díez-Córdova, Lucía T.
UNSPECIFIED
Troulé, Kevin
UNSPECIFIED
Weninger, Wolfgang
UNSPECIFIED
Wagner, Erwin F.
UNSPECIFIED
Last Modified: 21 Dec 2020 23:25
URI: https://eprints.centenary.org.au/id/eprint/139

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