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Adverse Events of anti-EGFR Therapy are Triggered by Hair Eruption and Commensal Skin Microbiota

ABSTRACT: Adverse Events of anti-EGFR Therapy are Triggered by Hair Eruption and Commensal Skin Microbiota

PROVIDER: PRJNA489001 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR7779070.fastq.gz	Fastqsanger.gz
	SRR7779080.fastq.gz	Fastqsanger.gz
	SRR7779090.fastq.gz	Fastqsanger.gz
	SRR7779100.fastq.gz	Fastqsanger.gz
	SRR7779110.fastq.gz	Fastqsanger.gz

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Adverse Events of anti-EGFR Therapy are Triggered by Hair Eruption and Commensal Skin Microbiota

Project description:EGFR targeted anti-cancer therapy induces severe skin toxicities, which affect life quality in patients. The lack of mechanistic details underlying these adverse events hampers their effective management. Here we identified EGFR as the epidermal master-regulator of the ERK pathway, which secures skin barrier integrity upon hair eruption. EGFR deficient epidermis displays a Th2-dominated expression signature and is permissive for excessive microbiota outgrowth. In the absence of EGFR, opening of the follicular ostia during hair eruption allows invasion of commensal microbiota aggravating barrier disruption and initiating an additional Th1 and Th17 response. Chronic folliculitis leads to Staphylococcus aureus dominated dysbiosis, further exacerbating inflammation and expanding barrier defects. Restoration of epidermal ERK signaling via therapeutic FGF7 treatment or transgenic SOS expression rescues skin barrier integrity in the absence of EGFR. These data reveal a gatekeeper function of the EGFR/ERK cascade in hair follicles securing the epidermal barrier around the erupting hair shaft.

2019-12-31 | GSE119376 | GEO

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Project description:Adverse Events of anti-EGFR Therapy are Triggered by Hair Eruption and Commensal Skin Microbiota

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Interactions with Commensal or Non-commensal Streptococci Alter Streptococcus mutans Transcriptome and Behaviors

Project description:RNA-Seq was used to compare the transcriptome of Streptococcus mutans UA159 during growth alone in monoculture, in coculture with Streptococcus gordonii DL1, Streptococcus sanguinis SK36 or Streptococcus oralis 34, and in a quadculture containing all four species. Individual cultures of commensal species Streptococcus gordonii DL1, Streptococcus sanguinis SK36 and Streptococcus oralis 34 were sequenced as well. This revealed a common transcriptome pattern in S. mutans when grown in mixed-species culture, indepenedent of the species identity that S. mutans was cultured with. Additionally, transcriptome changes in the commensal species could also be determined when undergoing competition from S. mutans. RNA-Seq was used to compare the transcriptome of Streptococcus mutans UA159 during growth alone in monoculture or in coculture with Streptococcus sobrinus NIDR 6715, Lactobacillus casei ATCC 4646 or Corynebacterium matruchotii ATCC 14266. These data were compared to previous coculture and quadculture RNA-Seq data with commensal streptococci (GSE209925). These data confirmed a common transcriptome pattern in S. mutans when grown in mixed-species culture with commensal streptococci that is not present with non-commensal streptococci, indepenedent of the species identity that S. mutans was cultured with.

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