Hair eruption initiates and commensal skin microbiota aggravate adverse events of anti-EGFR therapy

Result code in IS VaVaI
<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F61388971%3A_____%2F19%3A00518771" target="_blank" >RIV/61388971:_____/19:00518771 - isvavai.cz</a>
Result on the web
<a href="https://stm.sciencemag.org/content/11/522/eaax2693" target="_blank" >https://stm.sciencemag.org/content/11/522/eaax2693</a>
DOI - Digital Object Identifier
<a href="http://dx.doi.org/10.1126/scitranslmed.aax2693" target="_blank" >10.1126/scitranslmed.aax2693</a>

Result language
angličtina
Original language name
Hair eruption initiates and commensal skin microbiota aggravate adverse events of anti-EGFR therapy
Original language description
Epidermal growth factor receptor (EGFR)-targeted anticancer therapy induces stigmatizing skin toxicities affecting patients' quality of life and therapy adherence. The lack of mechanistic details underlying these adverse events hampers their management. We found that EGFR/ERK signaling is required in LRIG1-positive stem cells during de novo hair eruption to secure barrier integrity and prevent the invasion of commensal microbiota and inflammatory skin disease. EGFR-deficient epidermis is permissive for microbiota outgrowth and displays an atopic-like T(H)2-dominated signature. The opening of the follicular ostia during hair eruption allows invasion of commensal microbiota into the hair follicle, initiating an additional T(H)1 and T(H)17 response culminating in chronic folliculitis. Restoration of epidermal ERK signaling via prophylactic FGF7 treatment or transgenic SOS expression rescues the barrier defect in the absence of EGFR, highlighting a therapeutic anchor point. These data reveal that commensal skin microbiota provoke atopic-like inflammatory skin diseases by invading into the follicular opening of erupting hair.
Czech name
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Czech description
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Type
J<sub>imp</sub> - Article in a specialist periodical, which is included in the Web of Science database
CEP classification
—
OECD FORD branch
30230 - Other clinical medicine subjects

Project
<a href="/en/project/NV15-30782A" target="_blank" >NV15-30782A: Changes in the microbiome composition as a risk factor in the development of psoriasis</a><br>
Continuities
I - Institucionalni podpora na dlouhodoby koncepcni rozvoj vyzkumne organizace

Publication year
2019
Confidentiality
S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů

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