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

Kód výsledku v 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>

Výsledek na webu

<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>

Jazyk výsledku

angličtina

Název v původním jazyce

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

Popis výsledku v původním jazyce

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.

Název v anglickém jazyce

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

Popis výsledku anglicky

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.

Druh

J_imp - Článek v periodiku v databázi Web of Science

CEP obor

—

OECD FORD obor

30230 - Other clinical medicine subjects

Projekt

<a href="/cs/project/NV15-30782A" target="_blank" >NV15-30782A: Změny ve složení mikrobiomu jako rizikový faktor v rozvoji psoriázy</a><br>

Návaznosti

I - Institucionalni podpora na dlouhodoby koncepcni rozvoj vyzkumne organizace

Rok uplatnění

2019

Kód důvěrnosti údajů

S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů

Název periodika

Science Translational Medicine

ISSN

1946-6234

e-ISSN

—

Svazek periodika

11

Číslo periodika v rámci svazku

522

Stát vydavatele periodika

US - Spojené státy americké

Počet stran výsledku

18

Strana od-do

2693

Kód UT WoS článku

000502343800005

EID výsledku v databázi Scopus

2-s2.0-85076430005