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

Uluckan, Ozge and Roediger, Ben (2019) Cutaneous Immune Cell-Microbiota Interactions Are Controlled by Epidermal JunB/AP-1. Cell Reports, 29 (4). 844-859.e3. ISSN 22111247

Abstract

Atopic dermatitis is a complex, multi-factorial inflammatory skin disease. Uluçkan et al. show that JunBΔep mice display several hallmarks of AD, including S. aureus colonization. The authors characterize the immune responses to S. aureus and show that the adaptive immune system is required for protection against S. aureus colonization.

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.

Item Type: Article
Keywords: AP-1 atopic dermatitis dysbiosis JunB microbiota skin inflammation type 2 immunity
Date Deposited: 28 Nov 2019 00:45
Last Modified: 28 Nov 2019 00:45
URI: https://oak.novartis.com/id/eprint/38413

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